Aza-proline effectively mimics l-proline stereochemistry in triple helical collagen.

The prevalence of l-amino acids in biomolecules has been shown to have teleological importance in biomolecular structure and self-assembly. Recently, biophysical studies have demonstrated that natural l-amino acids can be replaced with non-natural achiral aza-amino acids in folded protein structures such as triple helical collagen. However, the structural consequences of achiral aza-amino acid incorporation has not been elucidated in the context of any relevant folded biomolecule.

Structural Basis for Aza-Glycine Stabilization of Collagen.

Previously, we have demonstrated that replacement of the strictly conserved glycine in collagen with aza-glycine provides a general solution for stabilizing triple helical collagen peptides (Chenoweth, D. M.; et al.