CSB Cutting Lecture Series: Ronald T. Raines, PhD, Friday, May 16, 2025!
The Department of Chemical and Systems Biology Presents
Cutting Lecture Series
Ronald T. Raines
Firmenich Professor of Chemistry, MIT
Friday, May 16, 2025
12:30 PM – 1:30 PM (Pacific Time)
Munzer Auditorium
Talk Title: “Lessons from Collagen: Chemical Biology in the Extracellular Matrix”
Talk Description: Collagen is the most abundant protein in animals, including humans. A typical human body has 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 many (2S,4R)-hydroxyproline (Hyp) residues, resulting from the most prevalent post-translational modification in animals. Using synthetic collagen-mimetic peptides (CMPs) that contain (2S,4R)-4-fluoroproline and other subtly non-natural residues, we have shown that previously unappreciated forces—stereoelectronic effects—are 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 exert exquisite control over collagen stability. Especially promising are CMPs that anneal specifically to the damaged collagen triple helices in wound beds, fibrotic tissue, and the tumor microenvironment. 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 wounds, fibrosis, cancer, and other indications. The approach is akin to antibody–drug conjugates but with much simpler molecules and mechanisms of action.