Abstract
Alternating sequences of D and L residues in peptides are directly related to the formation of several kinds of regular helical conformations usually called β‐helices. The major feature of these structures is that they can be associated with the transmembrane ion‐conducting channel activity in some natural antibacterial peptides. The study of alternating D,L synthetic peptides is critical to understand how factors such as surrounding media, main chain length, type of side chain and terminal groups, among others, can determine the adoption of a specific kind of β‐helix. Early studies pointed out that the peptides Boc(D‐NLeuL‐NLeu)~6~D‐MeNLeL‐NleD‐NleL‐NleOMe (Boc: tert‐butyloxycarbonyl) and BocL‐Nle(D‐NleL‐Nle)~5~D‐MeNleL‐NleD‐NleL‐NleOMe adopt in chloroform a unique detectable conformation single β^4.4^‐ and double β^5.6^↑↓‐helix, respectively. The influence of terminal groups on the final stable conformation of N‐formylated peptides has been studied in this work. The initial basic NMR data analysis of a synthetic alternating D,L‐oligopeptide with ten norleucines, N‐methylated on the residue 7 and having HCO and OMe as terminal groups clearly indicates the coexistence of two different conformations in equilibrium. NMR data and molecular dynamics calculations point to a dimeric antiparallel β‐helix structure β^5.6^↑↓ for the main conformation. On the other hand, NMR data suggest a single β‐helix structure β^4.4^ for the second conformation. Finally, a thermodynamic analysis of the equilibrium between both conformations has been carried out by one‐dimensional NMR measurements at ten different temperatures. The temperature at which 50% of dimer conformation is dissociated is 319 K. In addition, the dimer–monomer equilibrium curve obtained shows a Δ__G__>0 for the whole range of studied temperatures, and its behavior can be considered similar to the thermodynamic denaturation protein processes. © 2003 Wiley Periodicals, Inc. Biopolymers 73:229–241, 2004