β-Turns mediate diverse protein recognition processes, although dihedral angle preferences of canonical amino acids limit accessible β-turn geometries. Organic synthesis can go beyond these limitations and either increase the mobility of a β-turn or constrain it inside a bicyclic ring. Nine β-turn dipeptides are studied here in the isolated β-hairpin of the miniprotein Foldon, which is only moderately structured in the absence of the native protein environment. The dipeptide mimetics, which vary the backbone flexibility from linear alkyl chains to bicyclic dipeptides (Hot=Tap), are ranked against each other with regard to their hairpin-stabilizing capacities. NMR-derived parameters and melting temperatures correlate the backbone rigidity of the β-turns with the hairpin population. In contrast to the general expectation, highly populated hairpins are not only observed for rigid dipeptides, but also for selected flexible amino acids in the i + 1 and i + 2 positions of the β-turn.

Substitution of a peptide bond for an imine transforms the irreversible macrocyclization of peptides into a reversible process. The inherent cyclization tendency of a linear peptide is then analyzable through the equilibrium between the aldehyde and the imine by virtue of the higher reactivity of the corresponding linear peptide aldehyde. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the 18-membered macrocyclic imine expected. Herein, we analyzed this uncommon hemiaminal that shows that the biosynthesis of cyclic peptides is not necessarily based on linear precursor peptides with a high inherent macrolactamization tendency.

Dissecting proteins into their secondary structure elements (subdomains) should yield discrete peptide epitopes. However, β-hairpins detached from their natural protein environment usually lose their well-defined shape and, consequently, molecular recognition processes, such as antibody binding or protein interactions, are affected significantly. Thus, the isolated central β-hairpin (residues 12–24) of Foldon, the protein domain of this study, relaxes into a multitude of rotamers, although it still fulfills all necessary requirements to fold into a highly twisted shape. Here, two stabilization strategies from either end of the antiparallel strands of the discrete hairpin are opposed to each other, which reconstitute its shape in solution. The local side chain to backbone cyclization by the twist-compatible bicyclic β-turn mimetic Hot=Tap is identified to be superior to macrocyclic disulfide cyclization, which provokes local structural distortions.

In ELISA-Tests zur Früherkennung von rheumatoider Arthritis (RA) dienen synthetische Filaggrin-Peptide als Antigene für rheumaspezifische Autoantikörper (“anti-citrullinated peptide antibody”, ACPA). Hier wird ein Peptid vorgestellt, welches das Bindungsepitop von ACPA in Form einer stabil faltenden β-Haarnadel-Struktur präsentiert. NMR-Spektroskopie belegt die Homogenität der Faltung des Peptids, und so kann erstmals ein Strukturvorschlag für die antikörpergebundene Konformation des Epitops erstellt werden.

In the early detection of rheumatoid arthritis (RA) synthetic filaggrin peptides serve as antigens for rheumatoid-specific autoantibodies (anti-citrullinated peptide antibody, ACPA) in ELISA tests. In this work we present a peptide that exhibits the binding epitope of ACPA in the form of a stable folding β-hairpin. The homogeneity of the peptide folding was confirmed by NMR spectroscopy and might lead to the first proposed structure of the antibody-bound conformation of the epitope.

Synthetic oligopeptides containing polyhydroxylated bicyclic dipeptide (GlcTap) are investigated for their adhesion properties. The non-natural amino acid building block composed of GlcTap is derived from glucuronic acid and mimics the hydroxyl-amino acids of the natural proteins. Peptide oligomers of GlcTap flanked by the amino acids Tyr and Lys were synthesized and characterized. Solution structural studies performed by circular dichromism spectroscopy suggests that poly(LysGlcTapTyr) and poly(GlcTapTyr) adopts extended helical structures. Adhesion of these oligomers to the mica surface is shown by atomic force microscopy spectroscopy. Studies indicate that extended polyproline II polyhydroxylated peptide chains, which bear additional phenolic as well as cationic side chains, can mimic some of the adhesion properties of the natural protein models. Furthermore, obtained data suggest that poly(GlcTapTyr) and poly(LysGlcTapTyr) as outstanding adhesive compounds, which combine efficient synthetic accessibility with promising adhesive properties. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 273–281, 2013.