Solid-phase synthesis of short α-helices stabilized by the hydrogen bond surrogate approach.

Stabilized α-helices and nonpeptidic helix mimetics have emerged as powerful molecular scaffolds for the discovery of protein-protein interaction inhibitors. Protein-protein interactions often involve large contact areas, which are often difficult for small molecules to target with high specificity. The hypothesis behind the design of stabilized helices and helix mimetics is that these medium-sized molecules may pursue their targets with higher specificity because of a larger number of contacts. This protocol describes an optimized synthetic strategy for the preparation of stabilized α-helices that feature a carbon-carbon linkage in place of the characteristic N-terminal main-chain hydrogen bond of canonical helices. Formation of the carbon-carbon bond is enabled by a microwave-assisted ring-closing metathesis reaction between two terminal olefins on the peptide chain. The outlined strategy allows the synthesis and purification of a hydrogen bond surrogate (HBS) α-helix in ∼ 1 week.

Morphology controlled growth of chitosan-bound microtubes and a study of their biocompatibility and antibacterial activity.

Self-assembled peptide microtubes are fabricated with the biopolymer chitosan. The microtubes are covalently attached to chitosan and the morphology of the chitosan assembled on the surface of the microtubes can be tuned by altering the pH of the growth solution. Cytotoxicity studies in the presence of mouse embryonic fibroblasts indicate that the chitosan-bound microtubes are highly biocompatible and the cells are able to survive and proliferate at a similar rate to the control. Antibacterial studies in the presence of E. coli prove that the chitosan-bound microtubes are bactericidal. This simple method for the development of biocompatible microstructures will facilitate cell targeting, fabrication of efficient carrier devices, and the preparation of highly efficient antibacterial materials.