Why Proline? Influence of Ring-Size on the Collagen Triple Helix

Abstract

The effect of four- and six-membered ring-size analogs (azetidine- and piperidine-2-carboxylic acid, H-Aze-OH and H-Pip-OH) of proline on the stability of the collagen triple helix was examined. Computational and nuclear magnetic resonance spectroscopic studies with model compounds and thermal denaturation experiments with collagen peptides showed that the ring-size analogs destabilize the triple helix to a similar extent by either mismatching backbone dihedral angles ϕ and ψ (Pip) or by an unfavorable trans/cis amide bond ratio (Aze).