Structural Basis for Aza-Glycine Stabilization of Collagen.

Publication Type:

Journal Article


J Am Chem Soc, Volume 139, Issue 28, p.9427-9430 (2017)


Aza Compounds, Collagen, Glycine, Hydrogen Bonding, Models, Molecular, Molecular Structure, Peptides, Protein Folding, Temperature


<p>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. J. Am. Chem. Soc. 2016, 138, 9751 ; 2015, 137, 12422 ). The additional hydrogen bond and conformational constraints provided by aza-glycine increases the thermal stability and rate of folding in collagen peptides composed of Pro-Hyp-Gly triplet repeats, allowing for truncation to the smallest self-assembling peptide systems observed to date. Here we show that aza-glycine substitution enhances the stability of an arginine-containing collagen peptide and provide a structural basis for this stabilization with an atomic resolution crystal structure. These results demonstrate that a single nitrogen atom substitution for a glycine alpha-carbon increases the peptide&#39;s triple helix melting temperature by 8.6 &deg;C. Furthermore, we provide the first structural basis for stabilization of triple helical collagen peptides containing aza-glycine and we demonstrate that minimal alteration to the peptide backbone conformation occurs with aza-glycine incorporation.</p>