Heterotrimeric Peptide Models of Collagen

Deciphering the intricate structural and functional characteristics of heterotrimeric collagens relies on the development of heterotrimeric triple-helical peptide systems, yet incorporating three chains with distinct amino acid sequences remains challenging. This chapter offers a comprehensive exploration of heterotrimeric peptide models of collagen, covering their design, synthesis, and characterization methodologies. Various strategies, including Lys-Lys and Cys-Cys disulfide linkages, have been devised for covalently tethering heterotrimeric peptides. Additionally, it delves into the concept of charge-paired heterotrimeric peptides, detailing both AAB and ABC configurations and their implications for structural integrity and functionality. Computational simulation techniques are surveyed for refining heterotrimeric peptide design by precisely manipulating composition and register through optimization of pairwise interactions. Innovative Triblock peptides with three distinct domains are introduced, facilitating the creation of AAB-type and ABC-type heterotrimers with enhanced stability and greater flexibility in amino acid composition and arrangement. Lastly, the chapter explores covalent capture strategies for heterotrimeric peptides and provides insightful reflections on the current landscape and future trajectories of research in this dynamic field.