A minimalist design approach to antimicrobial agents based on a thionin template.

Numerous studies have been devoted to the stabilization of secondary structure elements to improve receptor-ligand recognition. We report a novel application of this principle to create new antimicrobial agents using the highly folded thionin from Pyrularia puberaas a template. Non-native disulfide bonds have been used to induce two short linear segments of the protein into an amphipathic helix.

The complete chirospectroscopic signature of the peptide 3(10)-helix in aqueous solution.

We synthesized by solution methods a water-soluble, terminally blocked heptapeptide based on five markedly helicogenic, C(alpha)-tetrasubstituted alpha-amino acids C(alpha)-methyl-L-norvalines and two strongly hydrophilic 2-amino-3-[1-(1,4,7-triazacyclononane)]-L-propanoic acid residues at positions 2 and 5. A Fourier transform infrared absorption and NMR analysis in deuterated chloroform and aqueous solutions of the heptapeptide and two side-chain protected synthetic precursors confirmed our working hypothesis that all oligomers are folded in the 3(10)-helical conformation. Based on these findings, we exploited this heptapeptide as a chiral reference compound for detailed electronic CD, vibrational CD, and Raman optical activity characterizations of the 3(10)-helix in aqueous solution.