Stroup A N, Rockwell A L, Gierasch L M
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
Biopolymers. 1992 Dec;32(12):1713-25. doi: 10.1002/bip.360321213.
In an effort to explore the residue preferences in three-residue reverse turns (so-called gamma-turns), two cyclic pentapeptides--cyclo(Gly1-Pro2-D-Phe3-Gly4-Ala5) (I) and cyclo(Gly1-Pro2-D-Phe3-Gly4-Val5) (II)--have been synthesized and analyzed by nmr. It was anticipated that the Gly-Pro-D-Phe-Gly portions of these molecules would favor a beta-turn conformation, leaving the remainder of the molecule to adopt a gamma turn, as seen in several previously studied model cyclic pentapeptides. The nmr data for both peptides in CDCl3 (5% DMSO-d6) and in neat DMSO-d6 indicate that the most populated conformation contains a distorted beta turn around Pro2-D-Phe3, which includes a gamma turn around D-Phe3. The distortion in the beta turn does not impede the formation of an inverse gamma turn around residue 5, and indeed, this conformation is observed in both peptides. Both the alanine and the bulkier valine residues are therefore found to be compatible with an inverse gamma turn. Molecular dynamics simulations on the title peptides are reported in the following paper. These simulations indicate that there is conformational flexibility around the D-Phe3-Gly4 peptide bond, which enables the formation of the gamma turn around D-Phe3. The third paper in this series explores the impact of a micellar environment on conformational equilibria in II.
为了探究三残基反向转角（即所谓的γ-转角）中的残基偏好，已合成了两种环五肽——环（甘氨酸1-脯氨酸2-D-苯丙氨酸3-甘氨酸4-丙氨酸5）（I）和环（甘氨酸1-脯氨酸2-D-苯丙氨酸3-甘氨酸4-缬氨酸5）（II），并通过核磁共振进行了分析。预计这些分子的甘氨酸-脯氨酸-D-苯丙氨酸-甘氨酸部分将有利于β-转角构象，使分子的其余部分采取γ-转角，正如在之前研究的几种模型环五肽中所观察到的那样。在CDCl3（5% DMSO-d6）和纯DMSO-d6中两种肽的核磁共振数据表明，最丰富的构象在脯氨酸2-D-苯丙氨酸3周围包含一个扭曲的β-转角，其中包括在D-苯丙氨酸3周围的一个γ-转角。β-转角中的扭曲并不妨碍在残基5周围形成反向γ-转角，实际上，在两种肽中都观察到了这种构象。因此发现丙氨酸和体积更大的缬氨酸残基都与反向γ-转角兼容。下一篇论文报道了对标题肽的分子动力学模拟。这些模拟表明，在D-苯丙氨酸3-甘氨酸4肽键周围存在构象灵活性，这使得能够在D-苯丙氨酸3周围形成γ-转角。本系列的第三篇论文探讨了胶束环境对II中构象平衡的影响。
