Three-residue turn in β-peptides nucleated by a 12/10 helix.

A new three-residue turn in β peptides nucleated by a 12/10-mixed helix is presented. In this design, β peptides were derived from the 1:1 alternation of C-linked carbo-β-amino acid ester [BocNH-(R)-β-Caa(r)-OMe] (Boc=tert-butyloxycarbonyl), which consisted of a D-ribo furanoside side chain, and β-hGly residues. The hexapeptide with (R)-β-Caa(r) at the N terminus showed the 'turn' stabilized by a 14-membered NH(4)⋅⋅⋅CO(6) hydrogen bond at the C terminus nucleated by a robust 12/10-mixed helix, thus providing a 'helix-turn' (HT) motif.

Design of β-amino acid with backbone-side chain interactions: stabilization of 14/15-helix in α/β-peptides.

A new C-linked carbo-β-amino acid, (R)-β-Caa((r)), having a carbohydrate side chain with D-ribo configuration, was prepared from D-glucose by inverting the C-3 stereocenter to introduce constraints/interactions. From the NMR studies it was inferred that the new monomer may participate in additional electrostatic interactions, facilitating and enhancing novel folds in oligomeric peptides derived from it. The α/β-peptides, synthesized from alternating L-Ala and (R)-β-Caa((r)), have shown the presence of 14/15-helix by NMR (in CDCl(3), methanol-d(3) and CD(3)CN), CD and MD calculations.