Local Control of the Cis鈥?i>Trans Isomerization and Backbone Dihedral Angles in Peptides Using Trifluoromethylated Pseudoprolines

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• 作者：Debby Feytens ; Gr茅gory Chaume ; G茅rard Chassaing ; Solange Lavielle ; Thierry Brigaud ; Byung Jin Byun ; Young Kee Kang ; Emeric Miclet
• 刊名：The Journal of Physical Chemistry B
• 出版年：2012
• 出版时间：April 5, 2012
• 年：2012
• 卷：116
• 期：13
• 页码：4069-4079
• 全文大小：352K
• 年卷期：v.116,no.13(April 5, 2012)
• ISSN：1520-5207

文摘

NMR studies and theoretical calculations have been performed on model peptides Ac-Ser(唯Pro)-NHMe, (S,S)Ac-Ser(唯^H,CF3Pro)-NHMe, and (R,S)Ac-Ser(唯^CF3,HPro)-NHMe. Their thermodynamic and kinetic features have been analyzed in chloroform, DMSO, and water, allowing a precise description of their conformational properties. We found that trifluoromethyl C^未-substitutions of oxazolidine-based pseudoprolines can strongly influence the cis鈥?i>trans rotational barriers with only moderate effects on the cis/trans population ratio. In CHCl₃, the configuration of the CF₃鈥揅^未 entirely controls the 蠄-dihedral angle, allowing the stabilization of 纬-turn-like or PPI/PPII-like backbone conformations. Moreover, in water and DMSO, this C^未-configuration can be used to efficiently constrain the ring puckering without affecting the cis/trans population ratio. Theoretical calculations have ascertained the electronic and geometric properties induced by the trifluoromethyl substituent and provided a rational understanding of the NMR observations.