O-acylation of hydroxyproline residues: Effect on peptide-bond isomerization and collagen stability

✍ Scribed by Cara L. Jenkins; Alexander I. McCloskey; Ilia A. Guzei; Eric S. Eberhardt; Ronald T. Raines

• Book ID: 101719312
• Publisher: Wiley (John Wiley & Sons)
• Year: 2005
• Tongue: English
• Weight: 194 KB
• Volume: 80
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20164

✦ Synopsis

Abstract

In collagen, strands of the sequence XaaYaaGly form a triple‐helical structure. The Yaa residue is often (2S,4__R__)‐4‐hydroxyproline (Hyp). The inductive effect of the hydroxyl group of Hyp residues greatly increases collagen stability. Here, electron withdrawal by the hydroxyl group in Hyp and its 4__S__ diastereomer (hyp) is increased by the addition of an acetyl group or trifluoroacetyl group. The crystalline structures of AcHyp[C(O)CH~3~]OMe and Achyp[C(O)CH~3~]OMe are similar to those of AcHypOMe and AcProOMe, respectively. The O‐acylation of AcHypOMe and AchypOMe increases the ^13^C chemical shift of its C^γ^ atom: AcHyp[C(O)CF~3~]OMe ≅ Achyp[C(O)CF~3~]OMe > AcHyp[C(O)CH~3~]OMe ≅ Achyp[C(O)CH~3~]OMe ≥ AcHypOMe ≅ AchypOMe. This increased inductive effect is not apparent in the thermodynamics or kinetics of amide bond isomerization. Despite apparently unfavorable steric interactions, (ProHypGly)~10~, which is O‐acylated with 10 acetyl groups, forms a triple helix that has intermediate stability: (ProHypGly)~10~ > {ProHyp[C(O)CH~3~]Gly}~10~ ≫ (ProProGly)~10~. Thus, the benefit to collagen stability endowed by the hydroxyl group of Hyp residues is largely retained by an acetoxyl group. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005