CONFORMATIONAL VERSATILITY OF THE N-ALPHA-ACYLATED TRIPEPTIDE AMIDE TAIL OF OXYTOCIN - SYNTHESIS AND CRYSTALLOGRAPHIC CHARACTERIZATION OF 3C-2(ALPHA)-BACKBONE MODIFIED, CONFORMATIONALLY RESTRICTED ANALOGS

The synthesis, physical and analytical characterization, and crystal-s tate structural analysis by X-ray diffraction of three analogues of th e N(alpha)-acylated tripeptide amide tail of oxytocin, each containing a cyclic C(alpha,alpha)-disubstituted glycine at position 2, have bee n performed. The peptides are Boc-L-Pro-AC3c-Gly-NH2, Z-L-Pro-Ac5c-Gly -NH2 and Z-L-Pro-AC6C-Gly-NH2. While the former is folded in a type-II beta-turn conformation at the -L-Pro-AC3C- sequence, the two latter t ripeptides form two consecutive (type-II, type-I') beta-turns. The Ac5 c- and AC6C-tripeptides are the first examples of such a highly folded structural combination in a position-2 analogue of the N(alpha)-acyla ted -L-Pro-L-Leu-Gly-NH2 sequence. (C) Munksgaard 1993.