Flores-Ortega Alejandra, Casanovas Jordi, Zanuy David, Nussinov Ruth, Alemán Carlos
Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain.
J Phys Chem B. 2007 May 17;111(19):5475-82. doi: 10.1021/jp0712001. Epub 2007 Apr 26.
The intrinsic conformational preferences of proline analogues having double bonds between carbon atoms in their rings have been investigated using quantum mechanical calculations at the B3LYP/6-31+G(d,p) level. For this purpose, the potential energy surface of the N-acety-N'-methylamide derivatives of three dehydroprolines (proline analogues unsaturated at alpha,beta; beta,gamma; and gamma,delta) and pyrrole (proline analogue with unsaturations at both alpha,beta and gamma,delta) have been explored, and the results are compared with those obtained for the derivative of the nonmodified proline. We found that the double bonds affect the ring puckering and the geometric internal parameters, even though the backbone conformation was influenced the most. Results indicate that the formation of double bonds between carbon atoms in the pyrrolidine ring should be considered as an effective procedure to restrict the conformational flexibility of prolines. Interestingly, we also found that the N-acetyl-N'-methylamide derivative of pyrrole shows a high probability of having a cis peptide bond preceding the proline analogue.
利用B3LYP/6-31+G(d,p)水平的量子力学计算，研究了在其环中碳原子之间具有双键的脯氨酸类似物的内在构象偏好。为此，探索了三种脱氢脯氨酸（在α,β；β,γ；和γ,δ处不饱和的脯氨酸类似物）和吡咯（在α,β和γ,δ处均不饱和的脯氨酸类似物）的N-乙酰基-N'-甲基酰胺衍生物的势能面，并将结果与未修饰脯氨酸衍生物的结果进行比较。我们发现，双键会影响环的褶皱和几何内部参数，尽管主链构象受到的影响最大。结果表明，在吡咯烷环中碳原子之间形成双键应被视为限制脯氨酸构象灵活性的有效方法。有趣的是，我们还发现吡咯的N-乙酰基-N'-甲基酰胺衍生物在脯氨酸类似物之前具有顺式肽键的可能性很高。
