NMR and Theoretical Calculations: A Unified View of the Cis/Trans Isomerization of 2-Substituted Thiazolidines Containing Peptides

The cis/trans isomerization of peptides containing the pseudoproline (4R)-thiazolidine-4-carboxylic acid Cys(ΨR1,R2 pro) is investigated from both an experimental and a theoretical point of view by NMR and DFT calculations. A series of Ac-Cys(ΨR1,R2 pro)-OCH3 and Ac-Cys(ΨR1,R2 pro)-NHCH3 peptides we...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2008-08, Vol.112 (32), p.9975-9981
Main Authors: Jamet, Helene, Jourdan, Muriel, Dumy, Pascal
Format: Article
Language:English
Subjects:
B: Biophysical Chemistry
Biochemistry, Molecular Biology
Biophysics
Chemical Sciences
Isomerism
Life Sciences
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular biology
Peptides - chemistry
Structural Biology
Thiazolidines - chemistry
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Summary:The cis/trans isomerization of peptides containing the pseudoproline (4R)-thiazolidine-4-carboxylic acid Cys(ΨR1,R2 pro) is investigated from both an experimental and a theoretical point of view by NMR and DFT calculations. A series of Ac-Cys(ΨR1,R2 pro)-OCH3 and Ac-Cys(ΨR1,R2 pro)-NHCH3 peptides were prepared to assess the influence of the substitution at the C2 position as well as of the amide following the thiazolidine residue. For each compound, the cis/trans ratio along with free energy, the puckering of the thiazolidine ring and the free rotational energy barrier are reported and discussed. We observe there is a pronounced effect of the C2 substituents and of the chirality upon the cis/trans ratio with the population of the cis content in the order (2R)-Cys(ΨCH3 ,H pro) < (2S)-Cys(ΨH,CH3 pro) < Cys(ΨCH3 ,CH3 pro). This is interpreted as a consequence of the steric effects imposed by the 2-methylation. For the dimethyl-substituted compounds our results revealed a destabilization of the trans conformers along with a lowering of the rotational trans to cis barrier. We also demonstrate that the introduction of methyl substituents on the thiazolidine cycle reduces the autocatalysis effect, and in particular that no autocatalysis occurs for the dimethyl derivative. A good agreement is obtained between all our experimental observations and our DFT calculations. It rationalizes the main effects which tailor the cis/trans isomerization.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp7118982