The Impact of 4-Thiaproline on Polyproline Conformation
The Impact of 4-Thiaproline on Polyproline Conformation
复制标题
DOI：
10.1021/jp503915p
复制
发表时间：
2014-09-18
影响因子：
3.3
通讯作者：
Horng, Jia-Cherng
中科院分区：
文献类型：
--
作者：
Lin, Yu-Ju;Chang, Chiao-Hsin;Horng, Jia-Cherng
脯氨酸在基因编码氨基酸中是独一无二的；由于存在饱和吡咯烷环，它比其他氨基酸更倾向于顺式肽键。脯氨酰肽键构象偏好可以通过改变环上的原子或取代基来调节。在简单的 Ac-Xaa-OMe 系统的研究中，(2R)-4-硫代脯氨酸 (Thp) 有利于内环褶皱和脯氨酰肽键。在此，为了研究Thp对更复杂的系统（即聚脯氨酸结构）的影响，我们制备了一系列具有一个或多个脯氨酸残基被Thp取代的聚脯氨酸肽，并使用圆二色性（CD）光谱来表征其结构。与使用 Ac-Xaa-OMe 系统获得的结果相反，我们发现 Thp 不仅使全反式聚脯氨酸 II 构象不稳定，而且也不利于全顺式聚脯氨酸 I 结构。基于混合密度泛函理论分析，我们证明这种现象可能是由于PPI螺旋中Thp的噻唑烷环的外型和内型褶皱之间的过渡势垒较小以及PPII构象中Thp的骨架n -> pi*相互作用较弱所致。实验和计算数据的结合使我们能够对 4-硫代脯氨酸对聚脯氨酸构象的影响获得新的见解。
Proline is unique among the genetically coded amino acids; because of the presence of a saturated pyrrolidine ring, it favors a cis peptide bond more strongly than other amino acids. The prolyl peptide bond conformational preference can be modulated by alterations to the atoms or substitution groups on the ring. In the study of a simple Ac-Xaa-OMe system, (2R)-4-thiaproline (Thp) was shown to favor an endo ring pucker and a as prolyl peptide bond. Herein, to investigate the effects of Thp on a more complex system, that is, the polyproline structure, we prepared a series of polyproline peptides with one or multiple proline residues substituted with Thp and used circular dichroism (CD) spectroscopy to characterize their structures. In contrast to the results obtained using the Ac-Xaa-OMe system, here we found that Thp not only destabilizes all-trans polyproline II conformation, but also disfavors all-cis polyproline I structure. On the basis of the hybrid density functional theory analysis, we demonstrate that this phenomenon could be due to the small transition barrier between an exo and an endo pucker for the thiazolidine ring of Thp in a PPI helix and a weak backbone n -> pi* interaction for Thp in PPII conformation. The combination of experimental and computational data allows us to gain new insights into the impact of 4-thiaproline on polyproline conformation.