Conformational preferences of alpha-substituted proline analogues.
DFT calculations at the B3LYP/6-31+G(d,p) level have been used to investigate how the replacement of the alpha hydrogen by a more sterically demanding group affects the conformational preferences of proline. Specifically, the N-acetyl-N'-methylamide derivatives of L-proline, L-alpha-methylproline, and L-alpha-phenylproline have been calculated, with both the cis/trans isomerism of the peptide bonds and the puckering of the pyrrolidine ring being considered. The effects of solvation have been evaluated by using a Self-Consistent Reaction Field model. As expected, tetrasubstitution at the alpha carbon destabilizes the conformers with one or more peptide bonds arranged in cis. The lowest energy minimum has been found to be identical for the three compounds investigated, but important differences are observed regarding other energetically accessible backbone conformations. The results obtained provide evidence that the distinct steric requirements of the substituent at C (alpha) may play a significant role in modulating the conformational preferences of proline.
Flores-Ortega
Alejandra
A
Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, 08028 Barcelona, Spain.
Jiménez
Ana I
AI
Cativiela
Carlos
C
Nussinov
Ruth
R
Alemán
Carlos
C
Casanovas
Jordi
J
D000107:Acetylation; D005740:Gases / Q000737:chemistry; D008745:Methylation; D008968:Molecular Conformation; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry
D005740:Gases; D011392:Proline