Effects of Glycosylation of (2<i>S</i>,4<i>R</i>)-4-Hydroxyproline on the Conformation, Kinetics, and Thermodynamics of Prolyl Amide Isomerization

Abstract

Glycosylation (galactosylation) of (2S,4R)-4-hydroxyproline (Hyp) in the peptide mimic N-acetyl-Hyp-N‘-methylamide does not mediate the isomer equilibrium nor the rate of isomerization between the cis- and trans-prolyl amides in water. However, glycosylation of Hyp results in a downfield shift (6.5−8 ppm) of the Cγ atom of proline that is consistent with an enhanced inductive effect. Moreover, NOE experiments on the α-and β-linked glycosylated AcHypNHMe amides indicate proximity between the galactose and pyrrolidine rings. This study strongly suggests that glycosylation of Hyp will have important implications on peptide backbone conformation