Structural Basis for Aza-Glycine Stabilization of Collagen Alexander J. Kasznel Yitao Zhang Yang Hai David M. Chenoweth 10.1021/jacs.7b03398.s001 https://acs.figshare.com/articles/journal_contribution/Structural_Basis_for_Aza-Glycine_Stabilization_of_Collagen/5179021 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. <i>J. Am. Chem. Soc.</i> <b>2016</b>, <i>138</i>, 9751; <b>2015</b>, <i>137</i>, 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’s triple helix melting temperature by 8.6 °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. 2017-06-26 00:00:00 self-assembling peptide systems peptide backbone conformation collagen peptides aza-glycine incorporation helical collagen peptides nitrogen atom substitution Aza-Glycine Stabilization Structural Basis arginine-containing collagen peptide Pro-Hyp-Gly triplet resolution crystal structure aza-glycine substitution glycine alpha-carbon increases aza-glycine increases hydrogen bond