Design of 尾-Amino Acid with Backbone鈥揝ide Chain Interactions: Stabilization of 14/15-Helix in 伪/尾-Peptides

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• 作者：Gangavaram V. M. Sharma ; Thota Anupama Yadav ; Madavi Choudhary ; Ajit C. Kunwar
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：August 17, 2012
• 年：2012
• 卷：77
• 期：16
• 页码：6834-6848
• 全文大小：731K
• 年卷期：v.77,no.16(August 17, 2012)
• ISSN：1520-6904

文摘

A new C-linked carbo-尾-amino acid, (R)-尾-Caa_(r), having a carbohydrate side chain with n class="smallcaps">dn>-ribo configuration, was prepared from n class="smallcaps">dn>-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 伪/尾-peptides, synthesized from alternating n class="smallcaps">ln>-Ala and (R)-尾-Caa_(r), have shown the presence of 14/15-helix by NMR (in CDCl₃, methanol-d₃ 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)路路路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鈥揵ackbone 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.