CONFORMATIONAL CHARACTERISTICS OF ALTERNATING STEREO-CO-OLIGOPEPTIDESOF D-NORLEUCINE AND L-NORLEUCINE - INFLUENCE OF AN N-METHYL GROUP

The conformational behavior of members of the series Boc-(L-Nle)(m)-(D -Nle-L-Nle)((n-m)/2)-OMe (m = 0 or 1; n = total number of residues) wi th n less than or equal to 12, and of analogs of comparable chain leng th having a NMe-group on the (n - 3)th residue has been investigated. The study has shown that D,L-alternating oligonorleucines behave very differently from stereo-co-oligopeptides of D-alloisoleucine and L-iso leucine, D- and L-valine, or D- and L-leucine. In particular, it has b een found that oligonorleucines do not form beta-helices as do the oth er oligopeptides. Instead, they form aggregates (very likely of the al pha-pleated sheet type), which are insoluble in common organic solvent s even al moderate chain lengths. In marked contrast with this behavio r, N-methylated analogs such as those studied, with n from 9 to 15, ca nnot generate very stable aggregates owing to the N-methyl group, and they prefer to form beta-helices. These beta-helices have been found b y solution H-1 NMR techniques to be almost exclusively of the types be ta(4.4) (single-stranded with about 4.4 residues per turn) and up down arrow beta(5.6) (double-stranded, antiparallel, with about 5.6 residu es per turn). (C) Munksgaard 1994.