title: Conformational and structural analysis of the equilibrium between single- and double-strand beta-helix of a D,L-alternating oligonorleucine.
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 beta-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 beta-helix. Early studies pointed out that the peptides Boc-(D-NLeu-L-NLeu)(6)-D-MeNLe-L-Nl-D-Nl-L-Nl-OMe (Boc: tert-butyloxycarbonyl) and Boc-L-Nle-(D-Nle-L-Nle)(5)-D-MeNle-L-Nle-D-Nle-L-Nle-OMe adopt in chloroform a unique detectable conformation single beta(4.4)- and double beta(5.6) upward arrow downward arrow -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 beta-helix structure beta(5.6) upward arrow downward arrow for the main conformation. On the other hand, NMR data suggest a single beta-helix structure beta(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 DeltaG>0 for the whole range of studied temperatures, and its behavior can be considered similar to the thermodynamic denaturation protein processes.
authors.affiliation: Departamento de Química Física, Facultat de Químicas, Universitat de Valencia, 46100-Burjassot, Valencia, Spain. Enrique.Navarro-Raga@uv.es
authors.forename: E
authors.initials: E
authors.lastname: Navarro
authors.forename: E
authors.initials: E
authors.lastname: Fenude
authors.forename: B
authors.initials: B
authors.lastname: Celda
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009646:Norleucine / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D004277:DNA, Single-Stranded; D009842:Oligopeptides; D009646:Norleucine; D004247:DNA