Design of beta-Amino Acid with Backbone-Side Chain Interactions: Stabilization of 14/15-Helix in alpha/beta-Peptides

作者：Sharma Gangavaram V M^*; Yadav Thota Anupama; Choudhary Madavi; Kunwar Ajit C

来源：Journal of Organic Chemistry, 2012, 77(16): 6834-6848.

DOI：10.1021/jo300865d

A new C-linked carbo-beta-amino acid, (R)-beta-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 alpha/beta-peptides, synthesized from alternating L-Ala and (R)-beta-Caa((r)), have shown the presence of 14/15-helix by NMR (in CDCl3, methanol-d(3) and CD3CN), CD and MD calculations. The hybrid peptides showed the presence of electrostatic interactions involving the intraresidue amide proton and the C3-OMe, which helped in the stabilization of the NH(i)center dot center dot center dot CO(i-4) H-bonds and adoption of 14/15-helix. The importance of such additional interactions has been well defined in recent times to stabilize the folding in a variety of peptidic foldamers. These observations suggest and emphasize that the side chain-backbone interactions are crucial in the stabilization of the desired folding propensity. The designed monomer thus enlarges the opportunities for the synthesis of peptides with novel conformations and expands the repertoire of the foldamers.

• 出版日期2012-8-17