University of Pennsylvania
Variation in the Xaa and Yaa Positions of Collagen Mimetic Peptides Containing Aza-Glycine
Protein folding is carefully regulated through intra- and intermolecular interactions between specific side chains and backbone functional groups of amino acids. Hydrogen bonding, along with a host of other weak interactions, serve to stabilize protein structure. Unnatural modifications to the protein backbone and side chains are commonly used to modulate the properties of proteins. An important class of unnatural peptide modifications are aza-amino acids, which are characterized by substitution of the α-carbon or some other adjacent position with nitrogen.
Some of these amino acid analogs exhibit a higher degree of planarity and restricted dihedral angles compared to natural amide linkages, making them valuable tools in peptide mimicry and structural studies. Mimetic peptides are indispensable for studying natural proteins such as collagen, the most abundant protein in mammals. The quaternary structure of collagen involves three individual protein strands intertwining to form a tightly packed triple helical bundle. Collagen’s primary structure are repeating, Xaa-Yaa-Gly, triplet sequences. Our group has previously shown the substitution of glycine residues with aza-glycine results in increased triple-helical thermal stability. Herein, we demonstrate the surprising contextual dependence of this increased stability based on the residues adjacent to the point of aza-glycine incorporation.