Müller G, Gurrath M, Kurz M, Kessler H
Organisch Chemisches Institut, Technische Universität München, Garching, Federal Republic of Germany.
Proteins. 1993 Mar;15(3):235-51. doi: 10.1002/prot.340150303.
To investigate the role of proline in defining beta turn conformations within cyclic hexa- and pentapeptides we synthesized and determined the conformations of a series of L- and D-proline-containing peptides by means of 2D NMR spectroscopy and restrained molecular dynamics simulations. Due to cis/trans isomerism the L-proline peptides adopt at least two different conformations that are analyzed and compared to the structures of the corresponding D-proline peptides. The cis conformations of the compounds cyclo(-Pro-Ala-Ala-Pro-Ala-Ala), cyclo(-Arg-Gly-Asp-Phe-Pro-Gly-), cyclo(-Arg-Gly-Asp-Phe-Pro-Ala-), cyclo (-Pro-Ala-Ala-Ala-Ala-), and cyclo(-Pro-Ala-Pro-Ala-Ala-) form uncommon beta VI turns that mimic the turn geometries found in crystallographically refined protein structures at such a detailed level that even preferred side chain orientations are reproduced. The ratios of the cis/trans isomers are analyzed in terms of the steric demand of the proline-following residue. The conformational details derived from this study illustrate the importance of the examination of small model compounds derived from protein loop regions, especially if bioactive recognition sequences, such as RGD (Arg-Gly-Asp), are incorporated.
为了研究脯氨酸在确定环状六肽和五肽内β-转角构象中的作用，我们合成了一系列含L-和D-脯氨酸的肽，并通过二维核磁共振光谱和受限分子动力学模拟确定了它们的构象。由于顺/反异构现象，L-脯氨酸肽至少采用两种不同的构象，并对其进行分析，与相应D-脯氨酸肽的结构进行比较。化合物环（-脯氨酸-丙氨酸-丙氨酸-脯氨酸-丙氨酸-丙氨酸）、环（-精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-脯氨酸-甘氨酸-）、环（-精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-脯氨酸-丙氨酸-）、环（-脯氨酸-丙氨酸-丙氨酸-丙氨酸-丙氨酸-）和环（-脯氨酸-丙氨酸-脯氨酸-丙氨酸-丙氨酸-）的顺式构象形成了不常见的βVI-转角，其在如此详细的水平上模拟了晶体学精制蛋白质结构中发现的转角几何形状，甚至再现了优选的侧链取向。根据脯氨酸之后残基的空间需求分析顺/反异构体的比例。这项研究得出的构象细节说明了检查源自蛋白质环区域的小模型化合物的重要性，特别是如果掺入了生物活性识别序列，如RGD（精氨酸-甘氨酸-天冬氨酸）。
