Conformational characteristics of alternating stereo-co-oligopeptides of D- 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) with n < or = to 12, and of analogs of comparable chain length 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-isoleucine, D- and L-valine, or D- and L-leucine. In particular, it has been found that oligonorleucines do not form beta-helices as do the other oligopeptides. Instead, they form aggregates (very likely of the alpha-pleated sheet type), which are insoluble in common organic solvents even at moderate chain lengths. In marked contrast with this behavior, N-methylated analogs such as those studied, with n from 9 to 15, cannot generate very stable aggregates owing to the N-methyl group, and they prefer to form beta-helices. These beta-helices have been found by solution 1H NMR techniques to be almost exclusively of the types beta 4.4 (single-stranded with about 4.4 residues per turn) and decreases increases beta 5.6 (double-stranded, antiparallel, with about 5.6 residues per turn).