Rules for the design of aza-glycine stabilized triple-helical collagen peptides

Abstract

Guidelines for incorporating aza-glycine residues in collagen peptides are presented, detailing their effects on triple-helical thermal stability.

Recent Advances in Collagen Mimetic Peptide Structure and Design

“…50 Meanwhile, Xaa substitutions following azGly (azG-Xaa-Hyp) are all destabilizing in comparison to Pro, and again, the most destabilizing are β-branched amino acids. 47 Incorporation of multiple azGly increased the triple helix T m with each substitution, particularly if substitutions were located in subsequent triplets on the peptide or centrally in the CMP. 51 Replacing all Gly in a CMP resulted in triple helices forming with as few as four triplets needed, compared to the minimum of seven typically needed for natural POG triplets.…”

“…51 Additionally, "clamping" the helix with az-Gly substitutions on either termini increases triple helix stability by an incredible 17−24 °C. 47,50 Thus, incorporation of azGly allows for tailoring CMPs of increased stabilities or shorter lengths than that of POG for various applications.…”

“…Similarly, azaglycine replaces the hydrophobic α-carbon CH 2 of Gly with NH of azGly. − Substitution of Gly to azGly into CMPs produced more stable triple helices by 10 °C with faster folding kinetics . There are two factors for why azGly improves triple helical fold while azPro does not.…”

“…Interestingly, aromatic amino acids in the Yaa position cause the greatest decrease in T m from Pro-Hyp-Gly, but have largest increase in T m (8–11 °C) when Gly is substituted with azG . Meanwhile, Xaa substitutions following azGly (azG-Xaa-Hyp) are all destabilizing in comparison to Pro, and again, the most destabilizing are β-branched amino acids . Incorporation of multiple azGly increased the triple helix T m with each substitution, particularly if substitutions were located in subsequent triplets on the peptide or centrally in the CMP .…”

Application of (4R)-aminoproline in peptide engineering: conformational bias and pH-responsiveness revisited

“…Decoration of the proline residues may endow collagen mimics with additional functions. [38][39][40] The incorporation of Amp, for instance, may create a highly polar collagen triple helix owing to the high polarity of the individual Amp residues (Fig. 3).…”