Conformational characteristics of alternating stereo‐co‐oligopeptides of D‐ and L‐norleucine: influence of an N‐methyl group

Abstract

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≤ 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 β‐helices as do the other oligopeptides. Instead, they form aggregates (very likely of the α‐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 β‐helices. These β‐helices have been found by solution 1H NMR techniques to be almost exclusively of the types β4,4 (single‐stranded with about 4.4 residues per turn) and ↓↑5,6 (double‐stranded, antiparallel, with about 5.6 residues per turn).

Study Of B-Sheet Helix Interactions Based On ConformationalProperties Of Synthetic D,L-Alternating Decapeptides

“…Several studies have indicated that the ion-conducting transmembrane channels formed by gramicidin A in lipid bilayer originated througha dimerization process, and Urry [1] has proposed that the channels are helical dimers consisting of two single stranded β-helices (6,3 residues per turn) connected head-to-head (formyl-end-to-formyl-end). Urry's proposal is consistent with a number of experimental observations, and the ability of single-and double-stranded β-helices to give head-to-head dimers has been demonstrated either with gramicidin A [1,2] as with synthetic N-formyl oligopeptides [3][4]. A previous work on elastin fragments has clearly revealed the presence of type I and type II β-turns.…”