Organic and Biomolecuar Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
J Org Chem. 2012 Aug 17;77(16):6834-48. doi: 10.1021/jo300865d. Epub 2012 Aug 8.
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. 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)···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.
一种新的 C 连接的碳-β-氨基酸，（R）-β-Caa((r))，具有 D-核糖构型的碳水化合物侧链，由 D-葡萄糖通过反转 C-3 立体中心来制备，以引入约束/相互作用。从 NMR 研究中推断，这种新的单体可能参与额外的静电相互作用，促进和增强源自它的寡肽的新折叠。通过 NMR（在 CDCl(3)、甲醇-d(3)和 CD(3)CN）、CD 和 MD 计算，从交替的 L-Ala 和 (R)-β-Caa((r))合成的 α/β-肽显示出 14/15-螺旋的存在。杂合肽显示出涉及残基内酰胺质子和 C3-OMe 的静电相互作用，这有助于稳定 NH(i)···CO(i-4) H 键和采用 14/15-螺旋。最近已经很好地定义了这种额外相互作用的重要性，以稳定各种肽折叠体中的折叠。这些观察结果表明并强调侧链-骨架相互作用对于稳定所需的折叠倾向至关重要。因此，设计的单体扩大了合成具有新型构象的肽的机会，并扩展了折叠体的范围。
