Conformational Preferences of α-Substituted Proline Analogues

Autor:	Carlos Alemán, Alejandra Flores-Ortega, Ruth Nussinov, Carlos Cativiela, Jordi Casanovas, Ana I. Jiménez
Rok vydání:	2008
Předmět:	chemistry.chemical_classification Steric effects Proline Chemistry Stereochemistry Organic Chemistry Molecular Conformation Substituent Solvation Acetylation Peptide Ring (chemistry) Methylation Article Pyrrolidine chemistry.chemical_compound Peptide bond Gases Conformational isomerism
Zdroj:	The Journal of Organic Chemistry. 73:3418-3427
ISSN:	1520-6904 0022-3263
DOI:	10.1021/jo702710x
Popis:	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.
Databáze:	OpenAIRE
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