Recent Advances in Collagen Mimetic Peptide Structure and Design

Collagen mimetic peptides (CMPs) fold into a polyproline type II triple helix, allowing the study of the structure and function (or misfunction) of the collagen family of proteins. This Perspective will focus on recent developments in the use of CMPs toward understanding the structure and controlling the stability of the triple helix. Triple helix assembly is influenced by various factors, including the single amino acid propensity for the triple helix fold, pairwise interactions between these amino acids, and long-range effects observed across the helix, such as bend, twist, and fraying. Important progress in creating a comprehensive and predictive understanding of these factors for peptides with exclusively natural amino acids has been made. In contrast, several groups have successfully developed unnatural amino acids that are engineered to stabilize the triple helical structure. A third approach to controlling the triple helical structure includes covalent cross-linking of the triple helix to stabilize the assembly, which eliminates the problematic equilibrium of unfolding into monomers and enforces compositional control. Advances in all these areas have resulted in significant improvements to our understanding and control of this important class of protein, allowing for the design and application of more chemically complex and well-controlled collagen mimetic biomaterials.