Sharma Gangavaram V M, Rao Kota Sudhakar, Ravi Rapolu, Narsimulu Kongari, Nagendar Pendem, Chandramouli Chirutha, Kumar Singarapu Kiran, Kunwar Ajit C
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Chem Asian J. 2009 Jan 5;4(1):181-93. doi: 10.1002/asia.200800249.
The design and synthesis of beta-peptides from new C-linked carbo-beta-amino acids (beta-Caa) presented here, provides an opportunity to understand the impact of carbohydrate side chains on the formation and stability of helical structures. The beta-amino acids, Boc-(S)-beta-Caa((g))-OMe 1 and Boc-(R)-beta-Caa((g))-OMe 2, having a D-galactopyranoside side chain were prepared from D-galactose. Similarly, the homo C-linked carbo-beta-amino acids (beta-hCaa); Boc-(S)-beta-hCaa((x))-OMe 3 and Boc-(R)-beta-hCaa((x))-OMe 4, were prepared from D-glucose. The peptides derived from the above monomers were investigated by NMR, CD, and MD studies. The beta-peptides, especially the shorter ones obtained from the epimeric (at the amine stereocenter C(beta)) 1 and 2 by the concept of alternating chirality, showed a much smaller propensity to form 10/12-helices. This substantial destabilization of the helix could be attributed to the bulkier D-galactopyranoside side chain. Our efforts to prepare peptides with alternating 3 and 4 were unsuccessful. However, the beta-peptides derived from alternating geometrically heterochiral (at C(beta)) 4 and Boc-(R)-beta-Caa((x))-OMe 5 (D-xylose side chain) display robust right-handed 10/12-helices, while the mixed peptides with alternating 4 and Boc-beta-hGly-OMe 6 (beta-homoglycine), resulted in left-handed beta-helices. These observations show a distinct influence of the side chains on helix formation as well as their stability.
本文介绍了新型C-连接的碳β-氨基酸（β-Caa）的β-肽的设计与合成，为了解碳水化合物侧链对螺旋结构形成和稳定性的影响提供了契机。具有D-吡喃半乳糖侧链的β-氨基酸Boc-(S)-β-Caa((g))-OMe 1和Boc-(R)-β-Caa((g))-OMe 2由D-半乳糖制备。同样，由D-葡萄糖制备了同型C-连接的碳β-氨基酸（β-hCaa）；Boc-(S)-β-hCaa((x))-OMe 3和Boc-(R)-β-hCaa((x))-OMe 4。通过核磁共振、圆二色光谱和分子动力学研究对上述单体衍生的肽进行了研究。β-肽，特别是通过交替手性概念从（在胺立体中心C(β)处）差向异构的1和2获得的较短β-肽，形成10/12螺旋的倾向要小得多。螺旋的这种显著去稳定作用可归因于较大的D-吡喃半乳糖侧链。我们制备交替使用3和4的肽的努力未成功。然而，由几何上异手性（在C(β)处）交替的4和Boc-(R)-β-Caa((x))-OMe 5（D-木糖侧链）衍生的β-肽显示出强大的右手10/12螺旋，而交替使用4和Boc-β-hGly-OMe 6（β-高甘氨酸）的混合肽则形成左手β-螺旋。这些观察结果表明侧链对螺旋形成及其稳定性有明显影响。
