Conformational Profile of a Proline−Arginine Hybrid

详细信息    查看全文

• 作者：Guillermo Revilla-Lpez ; Ana I. Jimnez ; Carlos Cativiela ; Ruth Nussinov ; Carlos Alemn ; David Zanuy
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2010
• 出版时间：October 25, 2010
• 年：2010
• 卷：50
• 期：10
• 页码：1781-1789
• 全文大小：321K
• 年卷期：v.50,no.10(October 25, 2010)
• ISSN：1549-960X

文摘

The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named (^βPro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C^β position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N′-methylamide derivatives of the cis and trans isomers of (^βPro)Arg have been examined in the gas phase and in solution by B3LYP/6-31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-(^βPro)Arg exhibit a preference for the α_L conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.