Conformational Preferences of Proline Analogues with a Fused Benzene Ring

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• 作者：Javier G. Warren ; Guillem Revilla-Lpez ; Carlos Alemn ; Ana I. Jimnez ; Carlos Cativiela ; Juan Torras
• 刊名：Journal of Physical Chemistry B
• 出版年：2010
• 出版时间：September 16, 2010
• 年：2010
• 卷：114
• 期：36
• 页码：11761-11770
• 全文大小：322K
• 年卷期：v.114,no.36(September 16, 2010)
• ISSN：1520-5207

文摘

The intrinsic conformational preferences of indoline-2-carboxylic acid (Inc) and its α-methylated derivative (αMeInc) have been investigated using quantum mechanical calculations. Specifically, the behavior of their N-acetyl-N′-methylamide derivatives, Ac-l-Inc-NHMe and Ac-l-αMeInc-NHMe, has been explored at the B3LYP/6-31+G(d,p) level. Such amino acids are analogues of proline and (α-methyl)proline, respectively, bearing a benzene ring fused to the C^γ−C^δ bond of the five-membered pyrrolidine ring. The additional aromatic group has been shown to significantly restrict the conformational space available to these residues by reducing the flexibility of both the five-membered cycle and the peptide backbone. The fused benzene ring also plays a critical role in determining the cis−trans arrangement of the amide bond involving the pyrrolidine nitrogen, which is also modulated by the presence of the α-methyl group in the αMeInc derivative. Furthermore, the influence of the environment on the conformational propensities of these compounds has been evaluated by using both a self-consistent reaction field model and a recently developed interface in a hybrid QM/MM scheme, in which the solvent molecules are treated explicitly with classical mechanics while the solute is described by quantum mechanics at the density functional theory level.