GLY-X-Y TRIPEPTIDE FREQUENCIES IN COLLAGEN - A CONTEXT FOR HOST-GUESTTRIPLE-HELICAL PEPTIDES

The collagen triple-helix consists of a repeating (Gly-X-Y)(n) sequenc e. In theory, there are more than 400 possible Gly-X-Y triplets, but a nalysis of sequences from fibrillar and nonfibrillar collagens shows t hat only a limited set of triplets ape found in significant numbers, a nd many are never observed, The nonrandom frequency of Gly-X-Y triplet s makes it practical to experimentally approach the stability of much of the collagen sequence through the study of a Limited set of host-gu est peptides, In these peptides, individual Gly-X-Y triplets constitut e the guest, while the host consists of Gly-Pro-Hyp tripeptides. A set of host-guest peptides was designed to contain the most common nonpol ar and charged triplets found in collagen. All formed stable triple-he lices, with their melting temperature depending on the identity of the guest triplet. While including less than 10% of all possible triplets , the data set covers 50-60% of collagen sequences and provides a star ting point for establishing a stability scale to predict the relative stability of important collagen regions, such as the matrix metallopro teinase cleavage site or binding sites. (C) 1998 Academic Press.