Introduction Collagen consists of three polypeptide chains that fold into a triple helix. Each natural chain contains many repeats of the sequence: XaaYaaGly, in which a third of the Xaa and Yaa residues are (2S)-proline (Pro). The pucker of a proline ring can be influenced by electronegative substituents, such as the hydroxyl in the naturally occurring residue, (2S,4R)-4-hydroxyproline (Hyp) [...

UNDERSTANDING AND ENGINEERING THE COLLAGEN TRIPLE HELIX Matthew Donald Shoulders Under the supervision of Professor Ronald T. Raines At the University of Wisconsin-Madison This thesis presents a hypothesis-driven approach to collagen research that integrates the power of organic chemistry with the tools of biophysics to enhance our understanding of proline conformation and collagen structure an...

The hydroxylation of proline residues in collagen is the most common posttranslational modification in humans. The hydroxylation is stereoselective, affording (2S,4R)-4-hydroxyproline (Hyp) in the Yaa position of the canonical Xaa-Yaa-Gly triad and thereby bestowing marked stabilization upon the collagen triple helix.1 The means by which Hyp stabilizes collagen has engendered dispute. One hypot...

(4-Phenoxyphenylsulfonyl)methylthiirane (SB-3CT) is the selective inhibitor of matrix metalloproteinase 2 (MMP2). The inhibition mechanism of MMP2 by SB-3CT involves C-H deprotonation with concomitant opening of the three-membered heterocycle. In this study, the energetics of the deprotonation-induced ring-opening of (4-phenoxyphenylsulfinyl)methylthiirane, the sulfoxide analogue of SB-3CT, are...