Co-reporter:Pablo Ríos;Tiddo J. Mooibroek;Tom S. Carter;Christopher Williams;Miriam R. Wilson;Matthew P. Crump
Chemical Science (2010-Present) 2017 vol. 8(Issue 5) pp:4056-4061
Publication Date(Web):2017/05/03
DOI:10.1039/C6SC05399H
Carbohydrate receptors with a chiral framework have been generated by combining a tetra-aminopyrene and a C3-symmetrical triamine via isophthalamide spacers bearing water-solubilising groups. These “synthetic lectins” are the first to show enantiodiscrimination in aqueous solution, binding N-acetylglucosamine (GlcNAc) with 16 : 1 enantioselectivity. They also show exceptional affinities. GlcNAc is bound with Ka up to 1280 M−1, more than twice that measured for previous synthetic lectins, and three times the value for wheat germ agglutinin, the lectin traditionally employed to bind GlcNAc in glycobiological research. Glucose is bound with Ka = 250 M−1, again higher than previous synthetic lectins. The results suggest that chirality can improve complementarity to carbohydrate substrates and may thus be advantageous in synthetic lectin design.
Co-reporter:Hennie Valkenier, Christopher M. Dias, Craig P. Butts, Anthony P. Davis
Tetrahedron 2017 Volume 73, Issue 33(Issue 33) pp:
Publication Date(Web):17 August 2017
DOI:10.1016/j.tet.2017.04.064
A new approach to anionophore design combines a trans-decalin scaffold with flexible o-phenylene bis-urea side-arms. The scaffold preorganises the side-arms, which can fold to encompass anionic substrates. A prototype has been synthesised by coupling an o-aminophenyl urea to a decalin bis-isocyanate, and has been shown to be active for anion binding and transport. Modelling and NMR studies show that the unbound receptor is capable of intramolecular hydrogen bonding but can reorganise to form up to eight hydrogen bonds to a chloride anion.Download high-res image (262KB)Download full-size image
Co-reporter:Nestor Lopez Mora, Azadeh Bahreman, Hennie Valkenier, Hongyu Li, Thomas H. Sharp, David N. Sheppard, Anthony P. Davis and Alexander Kros
Chemical Science 2016 vol. 7(Issue 3) pp:1768-1772
Publication Date(Web):07 Jan 2016
DOI:10.1039/C5SC04282H
Synthetic anion transporters (anionophores) have potential as biomedical research tools and therapeutics. However, the efficient and specific delivery of these highly lipophilic molecules to a target cell membrane is non-trivial. Here, we investigate the delivery of a powerful anionophore to artificial and cell membranes using a coiled-coil-based delivery system inspired by SNARE membrane fusion proteins. Incorporation of complementary lipopeptides into the lipid membranes of liposomes and cell-sized giant unilamellar vesicles (GUVs) facilitated the delivery of a powerful anionophore into GUVs, where its anion transport activity was monitored in real time by fluorescence microscopy. Similar results were achieved using live cells engineered to express a halide-sensitive fluorophore. We conclude that coiled-coil driven membrane fusion is a highly efficient system to deliver anionophores to target cell membranes.
Co-reporter:Pradeep K. Mandal, Brice Kauffmann, Harry Destecroix, Yann Ferrand, Anthony P. Davis and Ivan Huc
Chemical Communications 2016 vol. 52(Issue 60) pp:9355-9358
Publication Date(Web):28 Jun 2016
DOI:10.1039/C6CC04466B
Using commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of X-ray quality single crystals and the elucidation at 1.08 Å resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains.
Co-reporter:Tiddo J. Mooibroek, Matthew P. Crump and Anthony P. Davis
Organic & Biomolecular Chemistry 2016 vol. 14(Issue 6) pp:1930-1933
Publication Date(Web):14 Jan 2016
DOI:10.1039/C6OB00023A
A new synthetic lectin features apolar surfaces provided by two different aromatic components (biphenyl and pyrenyl). Affinities up to 260 M−1 are recorded for carbohydrates in water. The desymmetrised design has potential for variation to give receptors with a broadened range of capabilities.
Co-reporter:Tom S. Carter;Dr. Tiddo J. Mooibroek;Patrick F. N. Stewart; Matthew P. Crump;Dr. M. Carmen Galan ; Anthony P. Davis
Angewandte Chemie International Edition 2016 Volume 55( Issue 32) pp:9311-9315
Publication Date(Web):
DOI:10.1002/anie.201603082
Abstract
Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all-equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K1>3000 m−1 for axially substituted mannosamine, whereas a positively charged version binds the important α-sialyl unit with K1≈1300 m−1.
Co-reporter:Tom S. Carter;Dr. Tiddo J. Mooibroek;Patrick F. N. Stewart; Matthew P. Crump;Dr. M. Carmen Galan ; Anthony P. Davis
Angewandte Chemie 2016 Volume 128( Issue 32) pp:9457-9461
Publication Date(Web):
DOI:10.1002/ange.201603082
Abstract
Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all-equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K1>3000 m−1 for axially substituted mannosamine, whereas a positively charged version binds the important α-sialyl unit with K1≈1300 m−1.
Co-reporter:Micke Lisbjerg; Hennie Valkenier; Bo M. Jessen; Hana Al-Kerdi; Anthony P. Davis;Michael Pittelkow
Journal of the American Chemical Society 2015 Volume 137(Issue 15) pp:4948-4951
Publication Date(Web):April 8, 2015
DOI:10.1021/jacs.5b02306
Biotin[6]uril hexaesters represent a new class of anionophores which operate solely through C—H···anion interactions. The use of soft H-bond donors favors the transport of less hydrophilic anions (e.g., Cl–, NO3–) over hard, stongly hydrated anions (e.g., HCO3– and SO42–). Especially relevant is the selectivity between chloride and bicarbonate, the major inorganic anions in biological systems.
Co-reporter:Evan M. Peck; Wenqi Liu; Graeme T. Spence; Scott K. Shaw; Anthony P. Davis; Harry Destecroix;Bradley D. Smith
Journal of the American Chemical Society 2015 Volume 137(Issue 27) pp:8668-8671
Publication Date(Web):June 24, 2015
DOI:10.1021/jacs.5b03573
A macrocyclic tetralactam host is threaded by a highly fluorescent squaraine dye that is flanked by two polyethylene glycol (PEG) chains with nanomolar dissociation constants in water. Furthermore, the rates of bimolecular association are very fast with kon ≈ 106–107 M–1 s–1. The association is effective under cell culture conditions and produces large changes in dye optical properties including turn-on near-infrared fluorescence that can be imaged using cell microscopy. Association constants in water are ∼1000 times higher than those in organic solvents and strongly enthalpically favored at 27 °C. The threading rate is hardly affected by the length of the PEG chains that flank the squaraine dye. For example, macrocycle threading by a dye conjugate with two appended PEG2000 chains is only three times slower than threading by a conjugate with triethylene glycol chains that are 20 times shorter. The results are a promising advance toward synthetic mimics of streptavidin/biotin.
Co-reporter:Hennie Valkenier, Christopher M. Dias, Kathryn L. Porter Goff, Ondřej Jurček, Rakesh Puttreddy, Kari Rissanen and Anthony P. Davis
Chemical Communications 2015 vol. 51(Issue 75) pp:14235-14238
Publication Date(Web):04 Aug 2015
DOI:10.1039/C5CC05737J
Tris-N-arylthioureas derived in one step from 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene are remarkably effective anion carriers. With optimised aryl substituents their activities come close to the best currently known, suggesting that they might find use as readily available standards in anion transport research.
Co-reporter:Charles M. Renney, Gaku Fukuhara, Yoshihisa Inoue and Anthony P. Davis
Chemical Communications 2015 vol. 51(Issue 46) pp:9551-9554
Publication Date(Web):06 May 2015
DOI:10.1039/C5CC02768C
Reports have suggested that polar porphyrins such as tetraphenylporphine tetrasulfonate (TPPS) can serve as carbohydrate receptors in water. Here we find that TPPS shows changes in UV-visible absorption when treated with glucose, but that these are best explained by altered aggregation states and not by formation of a closely-bound complex.
Co-reporter:Harry Destecroix;Charles M. Renney;Dr. Tiddo J. Mooibroek;Tom S. Carter;Patrick F. N. Stewart; Matthew P. Crump ; Anthony P. Davis
Angewandte Chemie International Edition 2015 Volume 54( Issue 7) pp:2057-2061
Publication Date(Web):
DOI:10.1002/anie.201409124
Abstract
Dendritic side chains have been used to modify the binding environment in anthracene-based synthetic carbohydrate receptors. Control of length, charge, and branching enabled the positioning of side-chain carboxylate groups in such a way that they assisted in binding substrates rather than blocking the cavity. Conformational degeneracy in the dendrimers resulted in effective preorganization despite the flexibility of the system. Strong binding was observed to glucosammonium ions in water, with Ka values up to 7000 M−1. Affinities for uncharged substrates (glucose and N-acetylglucosamine) were also enhanced, despite competition from solvent and the absence of electrostatic interactions.
Co-reporter:Harry Destecroix;Charles M. Renney;Dr. Tiddo J. Mooibroek;Tom S. Carter;Patrick F. N. Stewart; Matthew P. Crump ; Anthony P. Davis
Angewandte Chemie 2015 Volume 127( Issue 7) pp:2085-2089
Publication Date(Web):
DOI:10.1002/ange.201409124
Abstract
Dendritic side chains have been used to modify the binding environment in anthracene-based synthetic carbohydrate receptors. Control of length, charge, and branching enabled the positioning of side-chain carboxylate groups in such a way that they assisted in binding substrates rather than blocking the cavity. Conformational degeneracy in the dendrimers resulted in effective preorganization despite the flexibility of the system. Strong binding was observed to glucosammonium ions in water, with Ka values up to 7000 M−1. Affinities for uncharged substrates (glucose and N-acetylglucosamine) were also enhanced, despite competition from solvent and the absence of electrostatic interactions.
Co-reporter:Hennie Valkenier ; Luke W. Judd ; Hongyu Li ; Sabir Hussain ; David N. Sheppard
Journal of the American Chemical Society 2014 Volume 136(Issue 35) pp:12507-12512
Publication Date(Web):August 14, 2014
DOI:10.1021/ja507551z
Transmembrane anion carriers (anionophores) have potential in biological research and medicine, provided high activities can be obtained. There is particular interest in treating cystic fibrosis (CF), a genetic illness caused by deficient anion transport. Previous work has found that anionophore designs featuring axial ureas on steroid and trans-decalin scaffolds can be especially effective. Here we show that replacement of ureas by thioureas yields substantial further enhancements. Six new bis-thioureas have been prepared and tested for Cl–/NO3– exchange in 1-palmitoyl-2-oleoylphosphatidylcholine/cholesterol large unilamellar vesicles (LUVs). The bis-thioureas are typically >10 times more effective than the corresponding ureas and are sufficiently active that transport by molecules acting singly in LUVs is readily detected. The highest activity is shown by decalin 9, which features N-(3,5-bis(trifluoromethyl)phenyl)thioureido and octyl ester substituents. A single molecule of transporter 9 in a 200 nm vesicle promotes Cl–/NO3– exchange with a half-life of 45 s and an absolute rate of 850 chloride anions per second. Weight-for-weight, this carrier is only slightly less effective than CFTR, the natural anion channel associated with CF.
Co-reporter:Hennie Valkenier, Cally J. E. Haynes, Julie Herniman, Philip A. Gale and Anthony P. Davis
Chemical Science 2014 vol. 5(Issue 3) pp:1128-1134
Publication Date(Web):10 Jan 2014
DOI:10.1039/C3SC52962B
Despite extensive interest in transmembrane anion carriers (anionophores), the factors that govern activity are still only partly understood. Herein we report a study which identifies a new principle for anionophore design, that of “lipophilic balance”. A series of simple thioureas with identical molecular formulae has been prepared and assayed for chloride/nitrate transport activity in synthetic vesicles. The molecules differ only in the positioning of the phenylthiourea binding unit within an 11-carbon linear chain. They are shown to possess very similar lipophilicities and anion affinities, while a test for leaching establishes that they locate almost exclusively in the vesicle membranes. Notwithstanding their close similarities, activities across the series show >5-fold variation, peaking when the phenylthiourea group is centrally located. The results suggest that transport is favoured by a balanced array of lipophilic substituents, possibly because this arrangement facilitates transfer of the complexed anion into the apolar membrane interior.
Co-reporter:Leana Travaglini, Lydia N. Bridgland and Anthony P. Davis
Chemical Communications 2014 vol. 50(Issue 37) pp:4803-4805
Publication Date(Web):25 Mar 2014
DOI:10.1039/C4CC01256A
Amide-linked side-chains can substitute for esters in crystalline nanoporous steroidal ureas (NSPUs). This efficient conjugation method increases the versatility of NPSUs, and should aid the inclusion of complex functional units in the crystal channels.
Co-reporter:Germinal Magro, Robert E. S. Bain, Claire A. Woodall, Robert L. Matthews, Stephen W. Gundry, and Anthony P. Davis
Environmental Science & Technology 2014 Volume 48(Issue 16) pp:9624-9631
Publication Date(Web):July 18, 2014
DOI:10.1021/es502319n
The development of low-cost tests for Escherichia coli is hampered by the expense and limited choice of enzyme substrates. Most chromogenic substrates are required in costly amounts, while fluorogenic substrates require an additional apparatus (e.g., an ultraviolet lamp) to be detected. Herein, we propose an alternative chromogenic substrate, resorufin β-d-glucuronide (REG), which is exceptionally sensitive and may be employed in very small amounts. We show that REG can be produced similarly to other simple glucuronides and should therefore be no more expensive. The compound is used by both healthy and injured E. coli, resulting in a pronounced color change from orange to a bright pink. Because the released dye (resorufin) has a high extinction coefficient, substantially lower amounts are needed than for commercially available substrates. The potential of this substrate is demonstrated by a presence/absence test requiring just 0.1 mg of REG/100 mL of water sample, one hundredth of the quantity needed for common chromogenic substrates, with an estimated bulk cost of ≤0.1 U.S. cents/test. REG shows promise as a chromogenic substrate for E. coli detection and should be considered in the development of new water tests, especially for low-income settings.
Co-reporter:Juan M. Casas-Solvas, Joshua D. Howgego and Anthony P. Davis
Organic & Biomolecular Chemistry 2014 vol. 12(Issue 2) pp:212-232
Publication Date(Web):14 Nov 2013
DOI:10.1039/C3OB41993B
The pyrene nucleus is a valuable component for materials, supramolecular and biological chemistry, due to its photophysical/electronic properties and extended rigid structure. However, its exploitation is hindered by the limited range of methods and outcomes for the direct substitution of pyrene itself. In response to this problem, a variety of indirect methods have been developed for preparing pyrenes with less usual substitution patterns. Herein we review these approaches, covering methods which involve reduced pyrenes, transannular ring closures and cyclisations of biphenyl intermediates. We also showcase the diverse range of substituted pyrenes which have been reported in the literature, and can serve as building blocks for new molecular architectures.
Co-reporter:James A. Cooper;Steven T. G. Street ; Anthony P. Davis
Angewandte Chemie 2014 Volume 126( Issue 22) pp:5715-5719
Publication Date(Web):
DOI:10.1002/ange.201311071
Abstract
Transmembrane anion carriers (anionophores) have potential for biological activity, including the treatment of channelopathies such as cystic fibrosis. A new family of anionophores has been synthesized, in which three thiourea groups are mounted on a cyclohexane-based scaffold. Though conceptually related to earlier polycyclic systems, these molecules are simpler and far more accessible. Preorganization is somewhat reduced compared to earlier systems, and anion affinities are correspondingly lower. However, transport activities set new records. This surprising performance suggests a role for controlled flexibility in the design of transmembrane anion carriers.
Co-reporter:James A. Cooper;Steven T. G. Street ; Anthony P. Davis
Angewandte Chemie International Edition 2014 Volume 53( Issue 22) pp:5609-5613
Publication Date(Web):
DOI:10.1002/anie.201311071
Abstract
Transmembrane anion carriers (anionophores) have potential for biological activity, including the treatment of channelopathies such as cystic fibrosis. A new family of anionophores has been synthesized, in which three thiourea groups are mounted on a cyclohexane-based scaffold. Though conceptually related to earlier polycyclic systems, these molecules are simpler and far more accessible. Preorganization is somewhat reduced compared to earlier systems, and anion affinities are correspondingly lower. However, transport activities set new records. This surprising performance suggests a role for controlled flexibility in the design of transmembrane anion carriers.
Co-reporter:Hennie Valkenier and Anthony P. Davis
Accounts of Chemical Research 2013 Volume 46(Issue 12) pp:2898
Publication Date(Web):March 20, 2013
DOI:10.1021/ar4000345
The natural product Valinomycin is a well-known transmembrane cation carrier. Despite being uncharged, this molecule can extract potassium ions from water without counterions and ferry them through a membrane interior. Because it only transports positive ions, it is electrogenic, mediating a flow of charge across the membrane. Equivalent agents for anions would be valuable research tools and may have therapeutic applications, especially in the treatment of “channelopathies” such as cystic fibrosis. However, no such molecules have been found in nature.In this Account, we describe our research toward synthetic and rationally designed “anti- Valinomycins”. As our core approach to this problem, we used the steroid nucleus, provided by cholic acid, as a scaffold for the assembly of anion receptors. By positioning H-bond donors on this framework, especially urea and thiourea groups in conformationally constrained axial positions, we created binding sites capable of exceptionally high affinities (up to 1011 M–1 for R4N+Cl– in chloroform). The extended hydrocarbon surface of the steroid helped to maintain compatibility with nonpolar media. When we tested these “cholapods” for chloride transport in vesicles, they provided the first evidence for electrogenic anion transport mediated by electroneutral organic carriers: in other words, they are the first authenticated anti-Valinomycins. They also proved active in live cells that we grew and assayed in an Ussing chamber.In subsequent work, we have shown that the cholapods can exhibit very high activities, with transport observed down to carrier/lipid ratios of 1:250 000. We also understand some of the effects of structure on the activity of these molecules. For example, in most cases, powerful transporters also act as powerful receptors. On the other hand, some modifications which favor binding do not promote transport. We gained functional advantages by cyclizing the cholapod architecture, which encloses the anion binding site. We could also simplify the structure without compromising function. A steroid-inspired trans-decalin framework has proved highly effective and may lead to agents with practical advantages. Changing an ester side-chain in this system revealed a surprising effect, whereby increased length and/or lipophilicity resulted in substantially raised activity. Although much remains to be discovered about these anionophores, their high activities and intrinsic tuneabilities bode well for applications. In future work, we plan to develop and exploit these molecules as tools for biophysical research and to explore the possibility of useful biological activity.
Co-reporter:Ramalingam Natarajan ; Lydia Bridgland ; Anchalee Sirikulkajorn ; Ji-Hun Lee ; Mairi F. Haddow ; Germinal Magro ; Bakhat Ali ; Sampriya Narayanan ; Peter Strickland ; Jonathan P. H. Charmant ; A. Guy Orpen ; Neil B. McKeown ; C. Grazia Bezzu
Journal of the American Chemical Society 2013 Volume 135(Issue 45) pp:16912-16925
Publication Date(Web):October 22, 2013
DOI:10.1021/ja405701u
Previous work has shown that certain steroidal bis-(N-phenyl)ureas, derived from cholic acid, form crystals in the P61 space group with unusually wide unidimensional pores. A key feature of the nanoporous steroidal urea (NPSU) structure is that groups at either end of the steroid are directed into the channels and may in principle be altered without disturbing the crystal packing. Herein we report an expanded study of this system, which increases the structural variety of NPSUs and also examines their inclusion properties. Nineteen new NPSU crystal structures are described, to add to the six which were previously reported. The materials show wide variations in channel size, shape, and chemical nature. Minimum pore diameters vary from ∼0 up to 13.1 Å, while some of the interior surfaces are markedly corrugated. Several variants possess functional groups positioned in the channels with potential to interact with guest molecules. Inclusion studies were performed using a relatively accessible tris-(N-phenyl)urea. Solvent removal was possible without crystal degradation, and gas adsorption could be demonstrated. Organic molecules ranging from simple aromatics (e.g., aniline and chlorobenzene) to the much larger squalene (Mw = 411) could be adsorbed from the liquid state, while several dyes were taken up from solutions in ether. Some dyes gave dichroic complexes, implying alignment of the chromophores in the NPSU channels. Notably, these complexes were formed by direct adsorption rather than cocrystallization, emphasizing the unusually robust nature of these organic molecular hosts.
Co-reporter:Joshua D. Howgego, Craig P. Butts, Matthew P. Crump and Anthony P. Davis
Chemical Communications 2013 vol. 49(Issue 30) pp:3110-3112
Publication Date(Web):05 Mar 2013
DOI:10.1039/C3CC41190G
Bicyclic carbohydrate receptors are easier to synthesise than tri- or tetra-cyclic relatives, and are better adapted to bind monosaccharide residues with bulky appendages. Disaccharides containing β-glucosyl units are preferred substrates.
Co-reporter:Gururaj Joshi and Anthony P. Davis
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 30) pp:5760-5763
Publication Date(Web):13 Jun 2012
DOI:10.1039/C2OB25900A
Synthetic lectins are molecules designed for the challenging task of biomimetic carbohydrate recognition in water. Previous work has explored a family of such systems based on bi/terphenyl units as hydrophobic surfaces and isophthalamide spacers to provide polar binding groups. Here we report a related receptor which employs a new spacer, 2,5-bis-(aminomethyl)-pyrrole, with an alternative (A-D-A) set of H-bonding valencies. The modified spacer leads to significant changes in binding selectivity, including a preference for glucose over all other tested substrates.
Co-reporter:Bunyarithi Sookcharoenpinyo;Dr. Emmanuel Klein;Dr. Yann Ferr;Dr. D. Barney Walker;Dr. Peter R. Brotherhood;Dr. Chenfeng Ke;Dr. Matthew P. Crump ; Anthony P. Davis
Angewandte Chemie 2012 Volume 124( Issue 19) pp:4664-4668
Publication Date(Web):
DOI:10.1002/ange.201200447
Co-reporter:Bunyarithi Sookcharoenpinyo;Dr. Emmanuel Klein;Dr. Yann Ferr;Dr. D. Barney Walker;Dr. Peter R. Brotherhood;Dr. Chenfeng Ke;Dr. Matthew P. Crump ; Anthony P. Davis
Angewandte Chemie International Edition 2012 Volume 51( Issue 19) pp:4586-4590
Publication Date(Web):
DOI:10.1002/anie.201200447
Co-reporter:Sabir Hussain ; Peter R. Brotherhood ; Luke W. Judd
Journal of the American Chemical Society 2011 Volume 133(Issue 6) pp:1614-1617
Publication Date(Web):January 21, 2011
DOI:10.1021/ja1076102
Decalins bearing two axial −NHCONHAr substituents and an ester-linked alkyl side chain have been synthesized and studied as anion receptors and transporters. The design relates to steroid-based “cholapods” but is more compact and less intrinsically lipophilic. Transport rates depend on both NHAr and the alkyl side chain. High activities can be achieved; with optimal substitution, chloride-nitrate exchange across vesicle membranes is measurable at transporter/lipid ratios as low as 1:250 000.
Co-reporter:Nicholas P. Barwell and Anthony P. Davis
The Journal of Organic Chemistry 2011 Volume 76(Issue 16) pp:6548-6557
Publication Date(Web):July 6, 2011
DOI:10.1021/jo200755z
Contacts between aromatic surfaces and saccharide CH groups are common motifs in natural carbohydrate recognition. These CH−π interactions are modeled in “synthetic lectins” which employ oligophenyl units as apolar surfaces. Here we report the synthesis and study of new synthetic lectins with fluoro- and hydroxy-substituted biphenyl units, designed to explore the role of π-electron density in carbohydrate CH−π interactions. We find evidence that recognition can be moderated through electronic effects but that other factors such as cavity hydration are also important and sometimes predominant in determining binding strengths.
Co-reporter:Dr. Ramalingam Natarajan;Dr. Germinal Magro;Lydia N. Bridgl;Anchalee Sirikulkajorn;Dr. Sampriya Narayanan;Lloyd E. Ryan;Dr. Mairi F. Haddow; A. Guy Orpen;Dr. Jonathan P. H. Charmant;Dr. Andrew J. Hudson; Anthony P. Davis
Angewandte Chemie International Edition 2011 Volume 50( Issue 48) pp:11386-11390
Publication Date(Web):
DOI:10.1002/anie.201105216
Co-reporter:Dr. Ramalingam Natarajan;Dr. Germinal Magro;Lydia N. Bridgl;Anchalee Sirikulkajorn;Dr. Sampriya Narayanan;Lloyd E. Ryan;Dr. Mairi F. Haddow; A. Guy Orpen;Dr. Jonathan P. H. Charmant;Dr. Andrew J. Hudson; Anthony P. Davis
Angewandte Chemie 2011 Volume 123( Issue 48) pp:11588-11592
Publication Date(Web):
DOI:10.1002/ange.201105216
Co-reporter:Peter R. Brotherhood and Anthony P. Davis
Chemical Society Reviews 2010 vol. 39(Issue 10) pp:3633-3647
Publication Date(Web):11 Aug 2010
DOI:10.1039/B926225N
Anion binding and transport are important goals of supramolecular chemistry, especially in light of the potential for biological activity. Success depends on scaffolds which can preorganise polar functionality for anion recognition, and can maintain the right physical properties (e.g. solubility) to operate in the desired medium (e.g. a cell membrane). In this tutorial review we show how steroids, and in particular the bile acids, can provide good solutions to the problem. Not only do they provide rigid frameworks for mounting H-bond donor functionality, but their lipophilic nature ensures that they remain compatible with non-polar environments. Podands derived from cholic acid (cholapods) have proved especially useful, being tuneable, readily accessible and exceptionally powerful. For example, affinities up to 1011 M−1 have been measured for neutral cholapods binding chloride salts in chloroform. Steroid-based anion receptors can also display interesting selectivities, demonstrating the principle that discrimination improves with binding strength, and showing good enantioselectivities with chiral anions. The binding strength of cholapods and related systems allows them to act as transmembrane anion carriers. Again activity is exceptionally high, with measurable chloride transport at cholapod∶lipid ratios of just 1∶250000 in vesicle membranes. These steroidal systems may present a real opportunity for the development of useful biological activity based on anion transport.
Co-reporter:Luke W. Judd and Anthony P. Davis
Chemical Communications 2010 vol. 46(Issue 13) pp:2227-2229
Publication Date(Web):25 Feb 2010
DOI:10.1039/B927005A
Cyclosteroidal “cholaphane” anion transporters show increased activities compared to acyclic “cholapod” analogues.
Co-reporter:Ramalingam Natarajan Dr.;JonathanP.H. Charmant Dr.;A.Guy Orpen ;AnthonyP. Davis
Angewandte Chemie International Edition 2010 Volume 49( Issue 30) pp:5125-5129
Publication Date(Web):
DOI:10.1002/anie.201002418
Co-reporter:Ramalingam Natarajan Dr.;JonathanP.H. Charmant Dr.;A.Guy Orpen ;AnthonyP. Davis
Angewandte Chemie 2010 Volume 122( Issue 30) pp:5251-5255
Publication Date(Web):
DOI:10.1002/ange.201002418
Co-reporter:Anthony P. Davis
Organic & Biomolecular Chemistry 2009 vol. 7(Issue 18) pp:3629-3638
Publication Date(Web):05 Aug 2009
DOI:10.1039/B909856A
Carbohydrate recognition presents a difficult challenge to supramolecular chemists, especially in the natural medium of water. After two decades of research, it has at last been possible to develop biomimetic receptors which perform well in aqueous solution. The “temple” family of carbohydrate receptors bind substrates with all-equatorial substitution patterns (e.g.β-glucosyl, β-GlcNAc, β-cellobiosyl) in a manner which is quite similar to carbohydrate-binding proteins (lectins). Affinities match some lectin–carbohydrate interactions, and selectivities are high. These “synthetic lectins” have been used to elucidate the role of water in carbohydrate recognition, and may have potential as research tools for glycobiology.
Co-reporter:Yann Ferr Dr.;Emmanuel Klein Dr.;NicholasP. Barwell;MatthewP. Crump Dr.;Jesus Jiménez-Barbero ;Cristina Vicent Dr.;Geert-Jan Boons ;Sampat Ingale;AnthonyP. Davis
Angewandte Chemie International Edition 2009 Volume 48( Issue 10) pp:
Publication Date(Web):
DOI:10.1002/anie.200990042
Co-reporter:NicholasP. Barwell;MatthewP. Crump Dr. ;AnthonyP. Davis
Angewandte Chemie International Edition 2009 Volume 48( Issue 41) pp:7673-7676
Publication Date(Web):
DOI:10.1002/anie.200903104
Co-reporter:Yann Ferr Dr.;Emmanuel Klein Dr.;NicholasP. Barwell;MatthewP. Crump Dr.;Jesus Jiménez-Barbero ;Cristina Vicent Dr.;Geert-Jan Boons ;Sampat Ingale;AnthonyP. Davis
Angewandte Chemie 2009 Volume 121( Issue 10) pp:1807-1811
Publication Date(Web):
DOI:10.1002/ange.200804905
Co-reporter:Yann Ferr Dr.;Emmanuel Klein Dr.;NicholasP. Barwell;MatthewP. Crump Dr.;Jesus Jiménez-Barbero ;Cristina Vicent Dr.;Geert-Jan Boons ;Sampat Ingale;AnthonyP. Davis
Angewandte Chemie 2009 Volume 121( Issue 10) pp:
Publication Date(Web):
DOI:10.1002/ange.200990043
Co-reporter:Yann Ferr Dr.;Emmanuel Klein Dr.;NicholasP. Barwell;MatthewP. Crump Dr.;Jesus Jiménez-Barbero ;Cristina Vicent Dr.;Geert-Jan Boons ;Sampat Ingale;AnthonyP. Davis
Angewandte Chemie International Edition 2009 Volume 48( Issue 10) pp:1775-1779
Publication Date(Web):
DOI:10.1002/anie.200804905
Co-reporter:NicholasP. Barwell;MatthewP. Crump Dr. ;AnthonyP. Davis
Angewandte Chemie 2009 Volume 121( Issue 41) pp:7809-7812
Publication Date(Web):
DOI:10.1002/ange.200903104
Co-reporter:Vicente del Amo, Adam P. McGlone, José M. Soriano, Anthony P. Davis
Tetrahedron 2009 65(32) pp: 6370-6381
Publication Date(Web):
DOI:10.1016/j.tet.2009.06.018
Co-reporter:D. Barney Walker;Gururaj Joshi
Cellular and Molecular Life Sciences 2009 Volume 66( Issue 19) pp:3177-3191
Publication Date(Web):2009 October
DOI:10.1007/s00018-009-0081-8
The importance of carbohydrate recognition in biology, and the unusual challenges involved, have lead to great interest in mimicking saccharide-binding proteins such as lectins. In this review, we discuss the design of artificial carbohydrate receptors, focusing on those which work under natural (i.e. aqueous) conditions. The problem is intrinsically difficult because of the similarity between substrate (carbohydrate) and solvent (water) and, accordingly, progress has been slow. However, recent developments suggest that solutions can be found. In particular, the “temple” family of carbohydrate receptors show good affinities and excellent selectivities for certain all-equatorial substrates. One example is selective for O-linked β-N-acetylglucosamine (GlcNAc, as in the O-GlcNAc protein modification), while another is specific for β-cellobiosyl and closely related disaccharides. Both show roughly millimolar affinities, matching the strength of some lectin–carbohydrate interactions.
Co-reporter:Samuel D. Whitmarsh, Adrian P. Redmond, Valentina Sgarlata and Anthony P. Davis
Chemical Communications 2008 (Issue 31) pp:3669-3671
Publication Date(Web):17 Jun 2008
DOI:10.1039/B805777J
Cholic acid has been transformed into cyclotrimeric and cyclotetrameric toroidal amphiphiles with inward-directed ammonium substituents; the cyclotrimer 3b effects the transport of chloride anions across vesicle bilayer membranes.
Co-reporter:Emmanuel Klein, Yann Ferrand, Elizabeth K. Auty and Anthony P. Davis
Chemical Communications 2007 (Issue 23) pp:2390-2392
Publication Date(Web):13 Mar 2007
DOI:10.1039/B618776E
A new carbohydratereceptor possesses a C3-symmetric polar cavity capable of encapsulating disaccharides; binding to β-maltosyl is preferred, complementing previous systems which have favoured “all-equatorial” substrates.
Co-reporter:Yann Ferrand;Matthew P. Crump
Science 2007 Volume 318(Issue 5850) pp:619-622
Publication Date(Web):26 Oct 2007
DOI:10.1126/science.1148735
Abstract
Carbohydrate recognition is biologically important but intrinsically challenging, for both nature and host-guest chemists. Saccharides are complex, subtly variable, and camouflaged by hydroxyl groups that hinder discrimination between substrate and water. We have developed a rational strategy for the biomimetic recognition of carbohydrates with all-equatorial stereochemistry (β-glucose, analogs, and homologs) and have now applied it to disaccharides such as cellobiose. Our synthetic receptor showed good affinities, not unlike those of some lectins (carbohydrate-binding proteins). Binding was demonstrated by nuclear magnetic resonance, induced circular dichroism, fluorescence spectroscopy, and calorimetry, all methods giving self-consistent results. Selectivity for the target substrates was exceptional; minor changes to disaccharide structure (for instance, cellobiose to lactose) caused almost complete suppression of complex formation.
Co-reporter:Khadga M. Bhattarai, Vicente del Amo, Germinal Magro, Adam L. Sisson, Jean-Baptiste Joos, Jonathan P. H. Charmant, Anob Kantacha and Anthony P. Davis
Chemical Communications 2006 (Issue 22) pp:2335-2337
Publication Date(Web):15 May 2006
DOI:10.1039/B602415G
Cholic acid 1 has been converted into triamine 5 with the all-trans polycyclic allocholanoyl skeleton and co-directed, axial amino groups; the potential of this system as a scaffold is illustrated by conversion to a preorganised anion receptor.
Co-reporter:Adam L. Sisson, John P. Clare and Anthony P. Davis
Chemical Communications 2005 (Issue 42) pp:5263-5265
Publication Date(Web):22 Sep 2005
DOI:10.1039/B510768G
Steroid-based receptors with enclosed binding sites, formed from quaternary ammonium and macrocyclic bis-urea units, can substantially override the Hofmeister series in anion phase transfer experiments.
Co-reporter:Beth A. McNally, Atanas V. Koulov, Bradley D. Smith, Jean-Baptiste Joos and Anthony P. Davis
Chemical Communications 2005 (Issue 8) pp:1087-1089
Publication Date(Web):12 Jan 2005
DOI:10.1039/B414589E
A fluorescent assay based on the chloride-sensitive probe, lucigenin, is developed for monitoring chloride transport into vesicles, and used to compare the effectiveness of three steroid-derived transporters.
Co-reporter:Adam L. Sisson;Vicente del Amo Sanchez;Germinal Magro Dr.;Alex M. E. Griffin;Shilen Shah;Jonathan P. H. Charmant Dr.
Angewandte Chemie 2005 Volume 117(Issue 42) pp:
Publication Date(Web):7 OCT 2005
DOI:10.1002/ange.200502330
Kristalle mit weiten, robusten Kanälen sind selten, vor allem wenn sie durch Selbstorganisation ohne die Hilfe von Metallionen gebildet werden. Drei Kristalle, die auf einem gängigen Steroidmotiv beruhen, wurden hergestellt, deren Kanäle chiral und (aus)gerichtet sowie weit genug (>1 nm) sind, um eine Vielzahl an Gästen aufzunehmen (siehe Bild; rot: Sauerstoff, blau: Stickstoff, grün: Fluor).
Co-reporter:Marc R.M. Andreae, Anthony P. Davis
Tetrahedron: Asymmetry 2005 Volume 16(Issue 14) pp:2487-2492
Publication Date(Web):18 July 2005
DOI:10.1016/j.tetasy.2005.06.031
Peptides with prolyl N-termini, attached to a PEG–polystyrene (TG) synthesis resin, have been tested as heterogeneous catalysts for the aldol reaction between acetone and p-nitrobenzaldehyde. Proline directly attached to TG showed good activity but poor enantioselectivity. However, in combination with serine or threonine, the selectivity improved considerably. At −25 °C, the dipeptide H-Pro-Ser-NH-TG achieved 82% ee. The H-Pro-Ser/Thr dipeptides may be seen as self-contained ‘catalytic head-groups’ for the development of more sophisticated aldol organocatalysts.
Co-reporter:Emmanuel Klein Dr.;Matthew P. Crump Dr.
Angewandte Chemie 2005 Volume 117(Issue 2) pp:
Publication Date(Web):21 DEC 2004
DOI:10.1002/ange.200461409
Ein süßes Zentrum: Die meisten Kohlenhydrate fühlen sich in Wasser sehr wohl. Können sie überredet werden, es zu verlassen? Ja, wenn ihr neues Zuhause alle ihre Bedürfnisse befriedigt. Der wasserlösliche Rezeptor 1 (R=Polycarboxylat) bietet hydrophobe Oberflächen (blauviolett) für CH-Gruppen und Amidgruppen (rot) für polare Substituenten. Äquatorialsubstitution ist besonders willkommen, und das System zieht entsprechend β-Glucosyl (2) vor.
Co-reporter:Emmanuel Klein Dr.;Matthew P. Crump Dr.
Angewandte Chemie International Edition 2005 Volume 44(Issue 2) pp:
Publication Date(Web):21 DEC 2004
DOI:10.1002/anie.200461409
A sweet center: Most carbohydrates are supremely comfortable in water. Can they be tempted to leave? Yes, if their new home satisfies all their needs. The water-soluble receptor 1 (R=polycarboxylate) provides hydrophobic surfaces (purple) for CH groups and amide groups (red) for polar substituents. Equatorial substitution is especially well accommodated, and the system duly favors β-glucosyl (2).
Co-reporter:Adam L. Sisson, Vicente del Amo Sanchez, Germinal Magro, Alex M. E. Griffin, Shilen Shah, Jonathan P. H. Charmant,Anthony P. Davis
Angewandte Chemie International Edition 2005 44(42) pp:6878-6881
Publication Date(Web):
DOI:10.1002/anie.200502330
Co-reporter:Vicente del Amo, Laura Siracusa, Theodoros Markidis, Beatriz Baragaña, Khadga M. Bhattarai, Marta Galobardes, Gregorio Naredo, M. Nieves Pérez-Payán and Anthony P. Davis
Organic & Biomolecular Chemistry 2004 vol. 2(Issue 22) pp:3320-3328
Publication Date(Web):15 Oct 2004
DOI:10.1039/B412298D
Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50 : 1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in ∼40% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.
Co-reporter:Trinidad Velasco, Gregory Lecollinet, Theo Ryan and Anthony P. Davis
Organic & Biomolecular Chemistry 2004 vol. 2(Issue 5) pp:645-647
Publication Date(Web):26 Jan 2004
DOI:10.1039/B315447E
Dipicolinoyl spacer groups are used to control the conformational and H-bonding properties of tricyclic carbohydrate receptors 3 and 4. Binding selectivities are changed in relation to all-isophthaloyl system 1b.
Co-reporter:Adam L. Sisson, John P. Clare, Luke H. Taylor, Jonathan P. H. Charmant and Anthony P. Davis
Chemical Communications 2003 (Issue 17) pp:2246-2247
Publication Date(Web):31 Jul 2003
DOI:10.1039/B305261C
Preorganised urea groups moderate the anion-exchange properties of cationic receptor 2, favouring halide extraction and promoting anion transport through a bulk liquid membrane.
Co-reporter:Atanas V. Koulov;Timothy N. Lambert;Rameshwer Shukla;Mahim Jain;J. Middleton Boon;Bradley D. Smith Dr.;Hongyu Li Dr.;David N. Sheppard Dr.;Jean-Baptiste Joos Dr.;John P. Clare Dr.
Angewandte Chemie 2003 Volume 115(Issue 40) pp:
Publication Date(Web):15 OCT 2003
DOI:10.1002/ange.200351957
Hilfe beim Überwinden von Barrieren: Membrantransport, von neutralen Kationenrezeptoren wie Valinomycin wohlbekannt, konnte auch für die Anionen-bindenden „Cholapode“ nachgewiesen werden. Die Cholapode unterstützen das Ausströmen von Chloridionen aus Vesikeln durch einen Antiport-Mechanismus und vermitteln den Anionenfluss durch lebende Zellen, die als Epithelzellen gezüchtet wurden (siehe schematische Darstellung).
Co-reporter:Atanas V. Koulov;Timothy N. Lambert;Rameshwer Shukla;Mahim Jain;J. Middleton Boon;Bradley D. Smith Dr.;Hongyu Li Dr.;David N. Sheppard Dr.;Jean-Baptiste Joos Dr.;John P. Clare Dr.
Angewandte Chemie International Edition 2003 Volume 42(Issue 40) pp:
Publication Date(Web):15 OCT 2003
DOI:10.1002/anie.200351957
Crossing the barriers: Membrane transport, a well-established phenomenon for neutral cation receptors such as valinomycin, has been demonstrated for the anion-binding “cholapods”. The cholapods promote chloride efflux from vesicles by an antiport mechanism and mediate anion flow through live cells grown as epithelia (see schematic representation).
Co-reporter:Grégory Lecollinet Dr.;Andrew P. Dominey Dr.;Trinidad Velasco
Angewandte Chemie International Edition 2002 Volume 41(Issue 21) pp:
Publication Date(Web):31 OCT 2002
DOI:10.1002/1521-3773(20021104)41:21<4093::AID-ANIE4093>3.0.CO;2-I
Selective oligosaccharide recognition remains a challenge for supramolecular chemistry. Tricyclic receptor 1 was designed to bind the all-equatorial β-cellobiosyl unit in 2. Remarkably, it succeeds while showing no detectable affinity for five other mono- and disaccharide substrates.
Co-reporter:Grégory Lecollinet Dr.;Andrew P. Dominey Dr.;Trinidad Velasco
Angewandte Chemie 2002 Volume 114(Issue 21) pp:
Publication Date(Web):4 NOV 2002
DOI:10.1002/1521-3757(20021104)114:21<4267::AID-ANGE4267>3.0.CO;2-4
Die selektive Oligosaccharid-Erkennung ist immer noch eine große Herausforderung für die supramolekulare Chemie. Der tricyclische Rezeptor 1 wurde entwickelt, um an die all-äquatoriale β-Cellobiose-Einheit von 2 zu binden. Dazu ist 1 in der Tat in der Lage, zeigt aber bemerkenswerterweise keine nachweisbare Affinität gegenüber fünf anderen Mono- und Disaccharid-Substraten.
Co-reporter:Beatriz Baragaña Dr.;Adrian G. Blackburn;Perla Breccia Dr. ;Javier de Mendoza ;José M. Padrón-Carrillo Dr.;Pilar Prados ;Jens Riedner;Johannes G. de Vries
Chemistry - A European Journal 2002 Volume 8(Issue 13) pp:
Publication Date(Web):24 JUN 2002
DOI:10.1002/1521-3765(20020703)8:13<2931::AID-CHEM2931>3.0.CO;2-H
The cationic steroidal receptors 9 and 11 have been synthesized from cholic acid 3. Receptor 9 extracts N-acetyl-α-amino acids from aqueous media into chloroform with enantioselectivities (L:D) of 7–10:1. The lipophilic variant 11 has been employed for the enantioselective transport of N-acetylphenylalanine, a) through dichloromethane (DCM) and dichloroethane (DCE) bulk liquid membranes (U-tube apparatus), and b) through 2.5 % (v/v) octanol/hexane via hollow fibre membrane contactors. Significant enantioselectivities and multiple turnovers were observed for both types of apparatus.
Co-reporter:Theo J. Ryan;Grégory Lecollinet;Trinidad Velasco
PNAS 2002 Volume 99 (Issue 8 ) pp:4863-4866
Publication Date(Web):2002-04-16
DOI:10.1073/pnas.062013499
We have previously shown that macrotricyclic host 1a is a powerful receptor for glucopyranosyl units in the nonpolar medium
of chloroform. However, the solubility properties of 1a did not permit studies of the extraction of carbohydrates from aqueous
solution. This paper describes the synthesis of the new variant 1b, furnished with a highly lipophilic exterior array of 12
benzyloxy substituents. In homogeneous solution, 1b behaves much as 1a, binding n-octyl β-d-glucoside with Ka = 720 M−1 in CD3OH/CDCl3 (8:92). In two-phase experiments, the improved solubility of 1b allows carbohydrate extraction to be observed. Three hexoses
(glucose, galactose, and mannose), two pentoses (ribose and xylose), and the two methyl glucosides are all extracted substantially
into chloroform from 1 M aqueous solutions. Among the hexoses, 1b shows notable affinity and selectivity for glucose, extracting
detectable amounts even from 0.1 M aqueous solutions.
Co-reporter:Alan J. Ayling;Shay Broderick;John P. Clare ;M. Nieves Pérez-Payán;Maarit Lahtinen;Maija J. Nissinen Dr.;Kari Rissanen
Chemistry - A European Journal 2002 Volume 8(Issue 9) pp:
Publication Date(Web):24 APR 2002
DOI:10.1002/1521-3765(20020503)8:9<2197::AID-CHEM2197>3.0.CO;2-J
The extraction-based protocol for measuring binding constants, developed by Cram and co-workers, has been extended for use with anionic substrates. The method is especially useful for high-affinity receptors, allowing very high binding constants to be measured in nonpolar solvents. Distribution constants Kd between chloroform and water have been obtained for tetraethylammonium chloride and bromide, thus calibrating the method for these two substrates. Application to steroidal podands 5–9 has confirmed the ability of electron-withdrawing groups to enhance hydrogen-bond donor capabilities. Binding constants of ≈3×107 M−1 have been measured for the most powerful receptor 7. An X-ray crystal structure of 15, the methyl ester analogue of 7, reveals a well-defined binding site preorganised for anion recognition.
Co-reporter:Laurence J. Lawless, Adrian G. Blackburn, Alan J. Ayling, M. Nieves Pérez-Payán and Anthony P. Davis
Organic & Biomolecular Chemistry 2001 (Issue 11) pp:1329-1341
Publication Date(Web):09 May 2001
DOI:10.1039/B009215K
Receptors 5–11, bearing guanidinium, carbamate and (in some cases) other functional groups, were synthesized from cholic acid 1. These cations were shown to extract chiral carboxylate anions from aqueous buffer into chloroform with significant enantioselectivities. The most successful receptors bore two carbamate substituents and achieved, in the best cases, ratios (L:D) of 7–10:1 for a series of five N-acetyl α-amino acids.
Co-reporter:Michael Müller Dr.;Trevor W. Mathers
Angewandte Chemie 2001 Volume 113(Issue 20) pp:
Publication Date(Web):10 OCT 2001
DOI:10.1002/1521-3757(20011015)113:20<3929::AID-ANGE3929>3.0.CO;2-3
Katalytisch aktive von inaktiven Kügelchen zu unterscheiden, das gelingt mit einer Methode, die auf der Fixierung der Kügelchen in einem Indikator-Gel basiert. Einen hohen praktischen Nutzen bietet eine Variante, bei der ein Säure-Base-Indikator eingesetzt wird, der die pH-Änderung beispielsweise bei der Esterhydrolyse anzeigt (siehe Bild): Beim Ansäuern fällt der Indikator unter Rotfärbung aus und erzeugt damit einen besonders kräftigen Kontrast zwischen den aktiven und den inaktiven Kügelchen.
Co-reporter:Michael Müller Dr.;Trevor W. Mathers
Angewandte Chemie International Edition 2001 Volume 40(Issue 20) pp:
Publication Date(Web):10 OCT 2001
DOI:10.1002/1521-3773(20011015)40:20<3813::AID-ANIE3813>3.0.CO;2-R
Catalytic beads are readily distinguished from inactive controls in a method which exploits the localizing potential of a gel. A useful variant employs an acid/base indicator to detect the pH change on ester hydrolysis (see picture). Precipitation of the acidified indicator (red) creates an especially strong contrast between active and inactive beads.
Co-reporter:Nestor Lopez Mora, Azadeh Bahreman, Hennie Valkenier, Hongyu Li, Thomas H. Sharp, David N. Sheppard, Anthony P. Davis and Alexander Kros
Chemical Science (2010-Present) 2016 - vol. 7(Issue 3) pp:NaN1772-1772
Publication Date(Web):2016/01/07
DOI:10.1039/C5SC04282H
Synthetic anion transporters (anionophores) have potential as biomedical research tools and therapeutics. However, the efficient and specific delivery of these highly lipophilic molecules to a target cell membrane is non-trivial. Here, we investigate the delivery of a powerful anionophore to artificial and cell membranes using a coiled-coil-based delivery system inspired by SNARE membrane fusion proteins. Incorporation of complementary lipopeptides into the lipid membranes of liposomes and cell-sized giant unilamellar vesicles (GUVs) facilitated the delivery of a powerful anionophore into GUVs, where its anion transport activity was monitored in real time by fluorescence microscopy. Similar results were achieved using live cells engineered to express a halide-sensitive fluorophore. We conclude that coiled-coil driven membrane fusion is a highly efficient system to deliver anionophores to target cell membranes.
Co-reporter:Pradeep K. Mandal, Brice Kauffmann, Harry Destecroix, Yann Ferrand, Anthony P. Davis and Ivan Huc
Chemical Communications 2016 - vol. 52(Issue 60) pp:NaN9358-9358
Publication Date(Web):2016/06/28
DOI:10.1039/C6CC04466B
Using commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of X-ray quality single crystals and the elucidation at 1.08 Å resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains.
Co-reporter:Pablo Ríos, Tiddo J. Mooibroek, Tom S. Carter, Christopher Williams, Miriam R. Wilson, Matthew P. Crump and Anthony P. Davis
Chemical Science (2010-Present) 2017 - vol. 8(Issue 5) pp:NaN4061-4061
Publication Date(Web):2017/03/30
DOI:10.1039/C6SC05399H
Carbohydrate receptors with a chiral framework have been generated by combining a tetra-aminopyrene and a C3-symmetrical triamine via isophthalamide spacers bearing water-solubilising groups. These “synthetic lectins” are the first to show enantiodiscrimination in aqueous solution, binding N-acetylglucosamine (GlcNAc) with 16:1 enantioselectivity. They also show exceptional affinities. GlcNAc is bound with Ka up to 1280 M−1, more than twice that measured for previous synthetic lectins, and three times the value for wheat germ agglutinin, the lectin traditionally employed to bind GlcNAc in glycobiological research. Glucose is bound with Ka = 250 M−1, again higher than previous synthetic lectins. The results suggest that chirality can improve complementarity to carbohydrate substrates and may thus be advantageous in synthetic lectin design.
Co-reporter:Tiddo J. Mooibroek, Matthew P. Crump and Anthony P. Davis
Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 6) pp:NaN1933-1933
Publication Date(Web):2016/01/14
DOI:10.1039/C6OB00023A
A new synthetic lectin features apolar surfaces provided by two different aromatic components (biphenyl and pyrenyl). Affinities up to 260 M−1 are recorded for carbohydrates in water. The desymmetrised design has potential for variation to give receptors with a broadened range of capabilities.
Co-reporter:Samuel D. Whitmarsh, Adrian P. Redmond, Valentina Sgarlata and Anthony P. Davis
Chemical Communications 2008(Issue 31) pp:NaN3671-3671
Publication Date(Web):2008/06/17
DOI:10.1039/B805777J
Cholic acid has been transformed into cyclotrimeric and cyclotetrameric toroidal amphiphiles with inward-directed ammonium substituents; the cyclotrimer 3b effects the transport of chloride anions across vesicle bilayer membranes.
Co-reporter:Anthony P. Davis
Organic & Biomolecular Chemistry 2009 - vol. 7(Issue 18) pp:NaN3638-3638
Publication Date(Web):2009/08/05
DOI:10.1039/B909856A
Carbohydrate recognition presents a difficult challenge to supramolecular chemists, especially in the natural medium of water. After two decades of research, it has at last been possible to develop biomimetic receptors which perform well in aqueous solution. The “temple” family of carbohydrate receptors bind substrates with all-equatorial substitution patterns (e.g.β-glucosyl, β-GlcNAc, β-cellobiosyl) in a manner which is quite similar to carbohydrate-binding proteins (lectins). Affinities match some lectin–carbohydrate interactions, and selectivities are high. These “synthetic lectins” have been used to elucidate the role of water in carbohydrate recognition, and may have potential as research tools for glycobiology.
Co-reporter:Leana Travaglini, Lydia N. Bridgland and Anthony P. Davis
Chemical Communications 2014 - vol. 50(Issue 37) pp:NaN4805-4805
Publication Date(Web):2014/03/25
DOI:10.1039/C4CC01256A
Amide-linked side-chains can substitute for esters in crystalline nanoporous steroidal ureas (NSPUs). This efficient conjugation method increases the versatility of NPSUs, and should aid the inclusion of complex functional units in the crystal channels.
Co-reporter:Charles M. Renney, Gaku Fukuhara, Yoshihisa Inoue and Anthony P. Davis
Chemical Communications 2015 - vol. 51(Issue 46) pp:NaN9554-9554
Publication Date(Web):2015/05/06
DOI:10.1039/C5CC02768C
Reports have suggested that polar porphyrins such as tetraphenylporphine tetrasulfonate (TPPS) can serve as carbohydrate receptors in water. Here we find that TPPS shows changes in UV-visible absorption when treated with glucose, but that these are best explained by altered aggregation states and not by formation of a closely-bound complex.
Co-reporter:Gururaj Joshi and Anthony P. Davis
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 30) pp:NaN5763-5763
Publication Date(Web):2012/06/13
DOI:10.1039/C2OB25900A
Synthetic lectins are molecules designed for the challenging task of biomimetic carbohydrate recognition in water. Previous work has explored a family of such systems based on bi/terphenyl units as hydrophobic surfaces and isophthalamide spacers to provide polar binding groups. Here we report a related receptor which employs a new spacer, 2,5-bis-(aminomethyl)-pyrrole, with an alternative (A-D-A) set of H-bonding valencies. The modified spacer leads to significant changes in binding selectivity, including a preference for glucose over all other tested substrates.
Co-reporter:Hennie Valkenier, Christopher M. Dias, Kathryn L. Porter Goff, Ondřej Jurček, Rakesh Puttreddy, Kari Rissanen and Anthony P. Davis
Chemical Communications 2015 - vol. 51(Issue 75) pp:NaN14238-14238
Publication Date(Web):2015/08/04
DOI:10.1039/C5CC05737J
Tris-N-arylthioureas derived in one step from 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene are remarkably effective anion carriers. With optimised aryl substituents their activities come close to the best currently known, suggesting that they might find use as readily available standards in anion transport research.
Co-reporter:Joshua D. Howgego, Craig P. Butts, Matthew P. Crump and Anthony P. Davis
Chemical Communications 2013 - vol. 49(Issue 30) pp:NaN3112-3112
Publication Date(Web):2013/03/05
DOI:10.1039/C3CC41190G
Bicyclic carbohydrate receptors are easier to synthesise than tri- or tetra-cyclic relatives, and are better adapted to bind monosaccharide residues with bulky appendages. Disaccharides containing β-glucosyl units are preferred substrates.
Co-reporter:Hennie Valkenier, Cally J. E. Haynes, Julie Herniman, Philip A. Gale and Anthony P. Davis
Chemical Science (2010-Present) 2014 - vol. 5(Issue 3) pp:NaN1134-1134
Publication Date(Web):2014/01/10
DOI:10.1039/C3SC52962B
Despite extensive interest in transmembrane anion carriers (anionophores), the factors that govern activity are still only partly understood. Herein we report a study which identifies a new principle for anionophore design, that of “lipophilic balance”. A series of simple thioureas with identical molecular formulae has been prepared and assayed for chloride/nitrate transport activity in synthetic vesicles. The molecules differ only in the positioning of the phenylthiourea binding unit within an 11-carbon linear chain. They are shown to possess very similar lipophilicities and anion affinities, while a test for leaching establishes that they locate almost exclusively in the vesicle membranes. Notwithstanding their close similarities, activities across the series show >5-fold variation, peaking when the phenylthiourea group is centrally located. The results suggest that transport is favoured by a balanced array of lipophilic substituents, possibly because this arrangement facilitates transfer of the complexed anion into the apolar membrane interior.
Co-reporter:Emmanuel Klein, Yann Ferrand, Elizabeth K. Auty and Anthony P. Davis
Chemical Communications 2007(Issue 23) pp:NaN2392-2392
Publication Date(Web):2007/03/13
DOI:10.1039/B618776E
A new carbohydratereceptor possesses a C3-symmetric polar cavity capable of encapsulating disaccharides; binding to β-maltosyl is preferred, complementing previous systems which have favoured “all-equatorial” substrates.
Co-reporter:Juan M. Casas-Solvas, Joshua D. Howgego and Anthony P. Davis
Organic & Biomolecular Chemistry 2014 - vol. 12(Issue 2) pp:NaN232-232
Publication Date(Web):2013/11/14
DOI:10.1039/C3OB41993B
The pyrene nucleus is a valuable component for materials, supramolecular and biological chemistry, due to its photophysical/electronic properties and extended rigid structure. However, its exploitation is hindered by the limited range of methods and outcomes for the direct substitution of pyrene itself. In response to this problem, a variety of indirect methods have been developed for preparing pyrenes with less usual substitution patterns. Herein we review these approaches, covering methods which involve reduced pyrenes, transannular ring closures and cyclisations of biphenyl intermediates. We also showcase the diverse range of substituted pyrenes which have been reported in the literature, and can serve as building blocks for new molecular architectures.
Co-reporter:Luke W. Judd and Anthony P. Davis
Chemical Communications 2010 - vol. 46(Issue 13) pp:NaN2229-2229
Publication Date(Web):2010/02/25
DOI:10.1039/B927005A
Cyclosteroidal “cholaphane” anion transporters show increased activities compared to acyclic “cholapod” analogues.
Co-reporter:Peter R. Brotherhood and Anthony P. Davis
Chemical Society Reviews 2010 - vol. 39(Issue 10) pp:NaN3647-3647
Publication Date(Web):2010/08/11
DOI:10.1039/B926225N
Anion binding and transport are important goals of supramolecular chemistry, especially in light of the potential for biological activity. Success depends on scaffolds which can preorganise polar functionality for anion recognition, and can maintain the right physical properties (e.g. solubility) to operate in the desired medium (e.g. a cell membrane). In this tutorial review we show how steroids, and in particular the bile acids, can provide good solutions to the problem. Not only do they provide rigid frameworks for mounting H-bond donor functionality, but their lipophilic nature ensures that they remain compatible with non-polar environments. Podands derived from cholic acid (cholapods) have proved especially useful, being tuneable, readily accessible and exceptionally powerful. For example, affinities up to 1011 M−1 have been measured for neutral cholapods binding chloride salts in chloroform. Steroid-based anion receptors can also display interesting selectivities, demonstrating the principle that discrimination improves with binding strength, and showing good enantioselectivities with chiral anions. The binding strength of cholapods and related systems allows them to act as transmembrane anion carriers. Again activity is exceptionally high, with measurable chloride transport at cholapod∶lipid ratios of just 1∶250000 in vesicle membranes. These steroidal systems may present a real opportunity for the development of useful biological activity based on anion transport.
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