Collagen mimetic peptides (CMPs) are a useful way to model the structure and function of the extracellular matrix (ECM). The interaction of collagen with ECM receptors, such as integrins, is dependent on the triple helical structure of collagen. However, the stability of supramolecular CMPs varies greatly depending on the overall peptide length, and the sequence identity. Also, the folding equilibrium of supramolecular CMPs results in both monomeric and triple helical peptides in solution. Covalent capture is an excellent tool to stabilize CMPs, as it does not disrupt the backbone of the peptide, and results in better stability and folding properties. We have designed a CMP with an integrin binding site, GFOGER, that can be covalently captured to effectively “lock” the triple helix. Upon covalent capture, the thermal stability and refolding properties were greatly improved. Covalent capture also improved the biomimetic properties of the peptide, and the covalently captured peptide was able to facilitate better cell adhesion compared a supramolecular helix with the same GFOGER motif. The mechanism of binding for this peptide was further investigated using <i>in vitro</i> assays with either EDTA / Mg<sup>2+</sup> or an anti α2β1 antibody. These treatments prevented the adhesion to the synthetic peptide, demonstrating that the binding event occurred between the GFOGER peptide, and the targeted α2β1 integrin. This peptide template improves upon current supramolecular models to mimic the bioactive sites of collagen in the ECM, and may be expanded to the design of biomaterials.

Covalent capture of collagen mimetic peptides (CMPs) to model the structure and function of integrin binding motifs

ACS Spring 2022

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