Modulating the conformational stability of triple-helical collagen by chemical modification

Collagen is composed of a triple helix of peptides with the sequence (XaaYaaGlY)n, where Xaa is often L-proline (Pro) and Yaa is often 4(R)-hydroxy-L-proline (Hyp). Each strand of collagen adopts a polyproline-II-Iike conformation. Natural collagen is found in approximately 19 different types, and is the most prevalent protein in animals. Triple helices comprised of the peptide (ProHypGly)lO have been studied extensively as a model for collagen. Previous work in our laboratory has shown that replacing the Hyp residues in (ProHypGly)1O with 4(R)-fluoro~L-pro1ine (FIp) residues increases dramatically the value of Tm' For example) in 50 mM acetic acid a (ProHypGly)1O triple helix has a Tm (which is the temperature at the midpoint of the thermal transition) of 69°C, whereas a (ProPlpGly)lO triple helix has a Tm of 91°C [lJ. We hypothesize that the greater electronwithdrawing ability of fluorine contributes to the greater conformational stability of (ProFlpGly)IO'