Co-reporter:Ping Li, Shiyu Sun, Alideertu Dong, Yanping Hao, Shuangqiang Shi, Zijia Sun, Ge Gao, Yuxin Chen
Applied Surface Science 2015 Volume 355() pp:446-452
Publication Date(Web):15 November 2015
DOI:10.1016/j.apsusc.2015.07.148
Highlights
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A novel antibacterial material, polyethylene glycol (PEG) and polyhexamethylene guanidine hydrochloride (PHGC) dual-polymer-functionalized graphene oxide (GO) (GO-PEG-PHGC), was synthesized.
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GO-PEG-PHGC had excellent antibacterial activity against E. coli and S. aureus.
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GO-PEG-PHGC shows enhanced antibacterial activity when compared to GO, GO-PEG or GO-PHGC alone, which was described to be related to a better dispersion of GO-PEG-PHGC in the presence of PEG.
Co-reporter:Tonghui Yi;Yibing Huang
Chemical Biology & Drug Design 2015 Volume 85( Issue 5) pp:598-607
Publication Date(Web):
DOI:10.1111/cbdd.12449
AN5-1 (YSKSLPLSVLNP) is an antimicrobial peptide isolated from the fermentation broth of Paenibacillus alvei strain AN5 (J Ind Microb Biotechnol 2013; 40: 571–9). In this study, we report the application of ubiquitin fusion technology to the expression and purification of AN5-1. Minimum inhibitory concentration (MIC) and measurement of hemolytic activity (MHC) were measured to confirm the biological activities of the expressed AN5-1. Bacterial cell membrane permeabilization was investigated to show the interaction between the AN5-1 and the bacterial cytoplasmic membrane. Furthermore, intracellular activities of the AN5-1 were determined by genomic DNA interaction assays. The results revealed AN5-1 damaging bacterial membranes and binding to bacterial genomic DNA to inhibit cellular functions, suggesting that it has multiple intracellular targets in bacteria. The application of ubiquitin fusion technology may be an excellent approach for industrial production to the expression and purification of antimicrobial peptide. Furthermore, AN5-1 was demonstrated as an antimicrobial peptide with great potentials, as bacterial resistance to AN5-1 would be not expected, due to the dual mechanisms of AN5-1 against bacteria.
Co-reporter:Yibing Huang;Liyan He;Guirong Li;Naicui Zhai;Hongyu Jiang
Protein & Cell 2014 Volume 5( Issue 8) pp:631-642
Publication Date(Web):2014 August
DOI:10.1007/s13238-014-0061-0
A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic α-helical antimicrobial peptide A12L/A20L (Ac-KWKSFLKTFKSLKKTVLHTLLKAISS-amide) was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activities of α-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitutions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram-positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial peptides with enhanced specificity.
Co-reporter:Yuping Shan, Jinfeng Huang, Juanjuan Tan, Gui Gao, Shuheng Liu, Hongda Wang and Yuxin Chen
Nanoscale 2012 vol. 4(Issue 4) pp:1283-1286
Publication Date(Web):03 Jan 2012
DOI:10.1039/C2NR11541G
To determine the effects of biophysical parameters (e.g. charge, hydrophobicity, helicity) of peptides on the mechanism of anticancer activity, we applied a single molecule technique—force spectroscopy based on atomic force microscope (AFM)—to study the interaction force at the single molecule level. The activity of the peptide and analogs against HeLa cells exhibited a strong correlation with the hydrophobicity of peptides. Our results indicated that the action mode between α-helical peptides and cancer cells was largely hydrophobicity-dependent.
Co-reporter:Alideertu Dong, Shi Lan, Jinfeng Huang, Tao Wang, Tianyi Zhao, Linghan Xiao, Weiwei Wang, Xin Zheng, Fengqi Liu, Ge Gao, and Yuxin Chen
ACS Applied Materials & Interfaces 2011 Volume 3(Issue 11) pp:4228
Publication Date(Web):October 18, 2011
DOI:10.1021/am200864p
Magnetic/antibacterial bifunctional nanoparticles were fabricated through the immobilization of antibacterial N-halamine on silica-coated Fe3O4-decorated poly(styrene-co-acrylate acid) (PSA) nanoparticles. The samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectra (XPS), X-ray diffraction (XRD), energy-dispersive X-ray spectrometry (EDX), Fourier transform infrared (FTIR), and thermogravimetric analysis (TGA). The N-halamine was developed from the precursor 5,5-dimethylhydantoin (DMH) by chlorination treatment, and experimental results showed that the loading amount of DMH on the silica-coated Fe3O4-decorated poly(styrene-co-acrylate acid) nanoparticles was adjustable. The as-synthesized nanoparticles exhibited superparamagnetic behavior and had a saturation magnetization of 18.93 emu g–1. Antibacterial tests showed that the resultant nanoparticles displayed enhanced antibacterial activity against both Gram-positive and Gram-negative bacteria compared with their bulk counterparts.Keywords: bifunctional; Fe3O4; N-halamine; nanoparticles; poly(styrene-co-acrylate acid); SiO2;
Co-reporter:Gui-Rong Li;Li-Yan He;Xiu-Ying Liu;Ai-Ping Liu;Yi-Bing Huang;Chao Qiu;Xiao-Yan Zhang;Jian-Qing Xu;Wei Yang;Yu-Xin Chen
Chemical Biology & Drug Design 2011 Volume 78( Issue 5) pp:835-843
Publication Date(Web):
DOI:10.1111/j.1747-0285.2011.01201.x
Lack of vaccines for HCV and HIV makes the antiviral drug development urgently needed. The recently identified HCV NS5A-derived virucidal peptide (C5A) demonstrated a wide spectrum of activities against viruses. In this study, the C5A sequence SWLRDIWDWICEVLSDFK was utilized as the framework to study the effect of the modulation of peptide helicity and hydrophobicity on its anti-HCV and anti-HIV activities. Peptide helicity and hydrophobicity were altered by substitutions of varying amino acids on the non-polar face of C5A. Peptide hydrophobicity has been proved to play a crucial role in peptide anti-HCV or anti-HIV activities. Peptide helicity was relatively independent with antiviral activity. However, peptide analogs with dimerized structure in an aqueous medium while maintaining the ability to be induced into a more helical structure in a hydrophobic environment may tend to show comparable or improved antiviral activity and specificity to C5A. By modulating peptide helicity and hydrophobicity, we improved the specificity of C5A against HCV and HIV by 23- and 69-fold, respectively, in terms of the ratio of hemolytic activity to antiviral activity. We demonstrated that obtained by de novo design approach, peptide I6L/I10L/V13L may be a promising candidate as a new anti-HCV and anti-HIV therapeutic.
Co-reporter:Yibing Huang;Jinfeng Huang
Protein & Cell 2010 Volume 1( Issue 2) pp:143-152
Publication Date(Web):2010 February
DOI:10.1007/s13238-010-0004-3
Antimicrobial peptides (AMPs), with their extraordinary properties, such as broad-spectrum activity, rapid action and difficult development of resistance, have become promising molecules as new antibiotics. Despite their various mechanisms of action, the interaction of AMPs with the bacterial cell membrane is the key step for their mode of action. Moreover, it is generally accepted that the membrane is the primary target of most AMPs, and the interaction between AMPs and eukaryotic cell membranes (causing toxicity to host cells) limits their clinical application. Therefore, researchers are engaged in reforming or de novo designing AMPs as a ‘singleedged sword’ that contains high antimicrobial activity yet low cytotoxicity against eukaryotic cells. To improve the antimicrobial activity of AMPs, the relationship between the structure and function of AMPs has been rigorously pursued. In this review, we focus on the current knowledge of α-helical cationic antimicrobial peptides, one of the most common types of AMPs in nature.
Co-reporter:Jinfeng Huang, Dianming Hao, Yu Chen, Yimin Xu, Juanjuan Tan, Yibing Huang, Fan Li, Yuxin Chen
Peptides (July 2011) Volume 32(Issue 7) pp:1488-1495
Publication Date(Web):1 July 2011
DOI:10.1016/j.peptides.2011.05.023
Enantiomeric amphipathic α-helical antibacterial peptides were synthesized and their biophysical and biological properties under different physiological conditions were studied. In the absence of physiological factors, the l- and d-peptides exhibited similar antimicrobial activities against a broad spectrum of bacteria, even against clinical isolates with resistance to traditional antibiotics. However, in the presence of NaCl, CaCl2 or human serum albumin (HSA) at physiological concentrations, the enantiomers revealed bacterium-species dependent attenuations in antibacterial activity. In the presence of salts the electrostatic interaction between the peptides and the biomembrane was inhibited. Salts, especially CaCl2, weakened the ability of the peptides to permeabilize the outer membrane of Gram-negative bacteria, as determined by a 1-N-phenylnaphthylamine uptake assay. HSA exhibited variable inhibitory effects on the activity of the peptides when incubated with different bacterial strains. The peptides showed different binding association abilities to HSA at different molar ratios, regardless of their chirality, resulting in reduced peptide biological activity. The d-peptide performed better than its l-enantiomer in all conditions tested because of its resistance to proteolysis, and may therefore represent a promising candidate for development as a therapeutic agent.Highlights► In the presence of NaCl, CaCl2 or human serum albumin at physiological concentrations, inhibitory effects of physiological conditions on antimicrobial activity of enantiomeric peptides have been investigated. ► The electrostatic interaction between peptides and biomembrane was inhibited in the presence of salts. ► Salts especially CaCl2 weakened the ability of peptides to permeabilize the outer membrane of Gram-negative bacteria. ► Peptide showed different binding association abilities to HSA at different molar ratios, which is irrelevant to the peptide chirality and caused the reduction of peptide antimicrobial activity. ► d-peptide showed better performance than its l-enantiomer in all tested conditions owing to its resistance against proteolysis, hence, may be a promising candidate as therapeutic in clinical practices.
