| Abstract
| - Acyclic dithiol and cyclic disulfide forms of the peptides Ac-Cys-Pro-Xaa-Cys-NH2 (Xaa = Phe,His, Tyr, Gly, and Thr) and Ac-Cys-Gly-Pro-Cys-NH2 and the peptide Ac-Ala-Gly-Pro-Ala-NH2 weresynthesized and characterized by mass spectrometry and NMR spectroscopy. Rate constants kct and ktcfor cis-to-trans and trans-to-cis isomerization, respectively, across the Cys-Pro or Gly-Pro peptide bondswere determined by magnetization transfer NMR techniques over a range of temperatures, and activationparameters were derived from the temperature dependence of the rate constants. It was found thatconstraints imposed by the disulfide bond confer an unexpected rate enhancement for cis/trans isomerization,ranging from a factor of 2 to 13. It is proposed that the rate enhancements are a result of an intramolecularcatalysis mechanism in which the NH proton of the Pro-Xaa peptide bond hydrogen bonds to the prolinenitrogen in the transition state. The peptides Ac-Cys-Pro-Xaa-Cys-NH2 and Ac-Cys-Gly-Pro-Cys-NH2 aremodel compounds for proline-containing active sites of the thioredoxin superfamily of oxidoreductaseenzymes; the results suggest that the backbones of the active sites of the oxidized form of these enzymesmay have unusual conformational flexibility.
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