Lessons from Collagen

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• Professor Ronald T. Raines, MIT
• Wednesday 24 May 2023, 14:00-15:00
• Pfizer Lecture Theatre, Department of Chemistry.

If you have a question about this talk, please contact Echo Wu Williamson.

Collagen is the most abundant protein in animals, including humans. A typical human body has over 10 pounds of collagen in its extracellular matrix. Dinosaurs also deployed collagen as their bodily scaffold. Collagen strands wind into a tight triple helix. Each strand contains (2S,4R)-4-hydroxyproline (Hyp) residues, resulting from the most prevalent post-translational modification in animals, as Hyp is more abundant in humans than seven of the twenty canonical amino acids. Using synthetic collagen-mimetic peptides (CMPs) that contain (2S,4R)-4-fluoroproline and other nonnatural residues, we have shown that a previously unappreciated force—stereoelectronic effects—is responsible for the increased stability endowed upon the collagen triple helix by its prevalent Hyp residues. This discovery led us to articulate the importance of C=O···C=O n-to-pi* interactions between main-chain carbonyl groups as a significant contributor to the conformational stability of not only collagen but all proteins. Exploiting these stereoelectronic effects with synthetic amino acids has enabled us to create collagen triple helices of extraordinary stability. Moreover, we have deployed principles of tessellation to self-assemble synthetic collagen triple helices of unprecedented length (~1 micrometer) from a single CMP . The ability to create stronger and longer collagen has myriad applications in biotechnology and biomedicine. Of special promise are CMPs that anneal specifically to the damaged collagen triple helices in fibrotic tissue, the environment surrounding solid tumors, and wound beds. This annealing can anchor pendant probes or chemotherapeutic agents at the site of collagen damage in vivo, providing new modalities for the clinical detection and treatment of fibrosis, cancer, wounds, and other indications.

This talk is part of the Biological Chemistry Research Interest Group series.

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