CONFORMATIONAL STUDY OF 2 LINEAR HEXAPEPTIDES BY 2-DIMENSIONAL NMR AND COMPUTER-SIMULATED MODELING - IMPLICATION FOR PEPTIDE CYCLIZATION INSOLUTION

Two linear peptides, L-prolyl-L-isoleucyl-L-valyl-L-alanyl-beta-alanin e (I) and L-isoleucyl-L-valyl-N-methyl-L-alanyl-beta-alanine (II), who se sequences were designed from protodestruxin and desmethyldestruxin B by replacing D-leucic acid with D-leucine, two cyclic hexadepsipepti des with insecticidal and immunodepressant activities, have been found to be cyclized in unusually high yields (>85%). In order to gain insi ght into the conformation and the relative flexibility of different co nstituent residues in these linear peptides, we have applied various t echniques of 2D-NMR spectroscopy coupled with dynamic simulated anneal ing by computer modeling to establish the solution conformations of th ese two linear peptides. Based on the derived structures, it is found that the distances between N- and c-terminal residues of both peptides are shea enough to facilitate the cyclization, thus collaborating the observation of favorable cyclization yields for both linear peptides. (C) 1996 Academic Press, inc.