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SUMMARY:Lessons from Collagen - Professor Ronald T. Raines\, MIT
DTSTART:20230524T130000Z
DTEND:20230524T140000Z
UID:TALK201376@talks.cam.ac.uk
CONTACT:Echo Wu Williamson
DESCRIPTION:Collagen is the most abundant protein in animals\, including h
 umans. A typical human body has over 10 pounds of collagen in its extracel
 lular matrix. Dinosaurs also deployed collagen as their bodily scaffold. C
 ollagen strands wind into a tight triple helix. Each strand contains (2S\,
 4R)-4-hydroxyproline (Hyp) residues\, resulting from the most prevalent po
 st-translational modification in animals\, as Hyp is more abundant in huma
 ns than seven of the twenty canonical amino acids. Using synthetic collage
 n-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 e
 ndowed 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* int
 eractions between main-chain carbonyl groups as a significant contributor 
 to the conformational stability of not only collagen but all proteins. Exp
 loiting these stereoelectronic effects with synthetic amino acids has enab
 led us to create collagen triple helices of extraordinary stability. Moreo
 ver\, we have deployed principles of tessellation to self-assemble synthet
 ic 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 fibrot
 ic tissue\, the environment surrounding solid tumors\, and wound beds. Thi
 s annealing can anchor pendant probes or chemotherapeutic agents at the si
 te of collagen damage in vivo\, providing new modalities for the clinical 
 detection and treatment of fibrosis\, cancer\, wounds\, and other indicati
 ons.
LOCATION:Pfizer  Lecture Theatre\,  Department of Chemistry
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