Synthesis and biological applications of collagen-model triple-helical peptides

Abstract

Triple-helical peptides (THPs) have been utilized as collagen models since the 1960s. The original focus for THP-based research was to unravel the structural determinants of collagen. In the last two decades, virtually all aspects of collagen structural biochemistry have been explored with THP models. More specifically, secondary amino acid analogs have been incorporated into THPs to more fully understand the forces that stabilize triple-helical structure. Heterotrimeric THPs have been utilized to better appreciate the contributions of chain sequence diversity on collagen function. The role of collagen as a cell signaling protein has been dissected using THPs that represent ligands for specific receptors. The mechanisms of collagenolysis have been investigated using THP substrates and inhibitors. Finally, THPs have been developed for biomaterial applications. These aspects of THP-based research are overviewed herein.

MMP-14 in skeletal muscle repair

“…The hydrophobic transmembrane domain, consisting of 24 amino acids, anchors MMP-14 to the cell membrane such that the C-terminal domain extends into the cytoplasm. The flexible proline-rich linker region facilitates association with substrates via its glycosylated sites and due to its role in appropriate orientation of both the catalytic and hemopexin domains (Fields 2010;Tochowicz et al 2011;Wu et al 2003). The amino acid sequence of the hemopexin domain is folded into a large, four b-bladed propeller-shaped structure.…”

Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage

“…The CII region containing the RG-TG(CIT) motif has a low content of proline and 4-hydroxyproline ( Figure 1A). Proline and 4-hydroxyproline stabilize the triple-helical structure, and a lack of these residues leads to a dynamically flexible and structurally distinct region of the protein (34).…”

Stabilization of Collagen-Model, Triple-Helical Peptides for In Vitro and In Vivo Applications

“…For several decades triple-helical peptides (THPs) or “mini-collagens” consisting of collagen-model sequences and their three-dimensional folds have been constructed and studied to fully investigate the structural and biological roles of collagenous proteins [5, 7–13]. A model for the collagen triple-helix was first proposed in the 1950s [14, 15] and subsequently refined over time [16–20].…”