Kato T, Mizuno H, Lee S, Aoyagi H, Kodama H, Go N, Kato T
Department of Chemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Int J Pept Protein Res. 1992 Jun;39(6):485-92.
The effect of ester bond on the conformation of peptide molecule was studied by designing and synthesizing a model tetradepsipeptide cyclo(-L-Ala-L-Hmb-)2 and by analyzing the conformation both theoretically and experimentally. Theoretical analysis showed that both ester and peptide bonds in the calculated low-energy conformations within 3 kcal/mol of the global minimum take a trans but distorted configuration. The distortion is larger in ester bonds than in peptide bonds. Further, the four carbonyls project from one side of the plane of the cyclic backbone, whereas the side chains project from the other side. These results are consistent with the experimental results obtained by NMR measurement; first, the coupling constant deduced from 1H-NMR species in DMSO-d6 is consistent with the dihedral angles of the calculated low-energy conformations; second, results of NOE measurement can reproduce the calculated configuration of the carbonyls and side chains. From the consistency between theoretical and experimental results, it is concluded that this model tetradepsipeptide takes an all-trans backbone conformation in solution and this backbone conformation is stabilized by large distortion in the ester bond, which compensates the strain resulted from the 12-membered cyclic backbone structure consisting only of L-residues.
通过设计和合成模型四环缩肽环（-L-丙氨酸-L-羟甲基丁二酸-）₂，并进行理论和实验分析，研究了酯键对肽分子构象的影响。理论分析表明，在全局最小值3千卡/摩尔范围内计算得到的低能量构象中，酯键和肽键均呈反式但扭曲的构型。酯键的扭曲程度大于肽键。此外，四个羰基从环状主链平面的一侧伸出，而侧链从另一侧伸出。这些结果与通过核磁共振测量获得的实验结果一致；首先，从DMSO-d₆中的¹H-NMR谱推导得到的耦合常数与计算得到的低能量构象的二面角一致；其次，NOE测量结果能够重现计算得到的羰基和侧链构型。根据理论和实验结果的一致性，得出该模型四环缩肽在溶液中采取全反式主链构象，且这种主链构象通过酯键中的大扭曲得以稳定，该扭曲补偿了仅由L-残基组成的12元环状主链结构所产生的应变。
