Design, Synthesis, Structural Studies, & Applications of Synthetic Collagen Peptides

Collagen is the principal structural protein in mammals, found in skin, bones, muscles, and organs. The objectives of this research were to 1) characterize and improve the biophysical properties of collagen by integrating non-natural amino acids, and 2) utilize these enhancements to design novel chemical tools. This was accomplished by synthesizing low molecular weight collagen model peptides (1-2 kDa) to determine the influence of aza-glycine (azGly, azG) and aza-proline (azPro, azP) on collagen’s structure, assembly, and stability. This work includes 1) the first definitive structural evidence that these collagen “aza-peptides” still assemble into the triple helix molecular topology critical for collagen’s structure, function, and application as a biomaterial, and 2) confirmation that collagen aza-peptides interact with native collagen matrices. The latter was achieved by designing and synthesizing an array of novel fluorescent collagen aza-peptide-based probes to visualize binding in biological samples. Collectively, this data validates the efficacy of collagen aza-peptides as chemical tools and provides a foundation for a range of future applications and structural studies