Solution structure of a D,L‐alternating oligonorleucine as a model of double‐stranded antiparallel β‐helix

Abstract

Conformational characteristics of alternating D,L linear peptides are of particular interest because of their capacity to form transmembrane channels with different transport properties, as some natural antibiotics do. Single- and double-stranded beta-helical structures are common for alternating D,L peptides. The stability of the beta-helix depends on several structural factors, such as the backbone peptide length, type and position of side chains, and nature of terminal groups. The NMR and molecular dynamics solution conformation of a synthetic alternating D,L-oligopeptide with 15 norleucines (XVMe) has been used as a model to get insight in to the conformational features of double-stranded beta-helix structures. The NH chemical shift values (delta(NH)) and long-range nuclear Overhauser effects (NOE) cross peaks, in particular interstrand connectivities, clearly point to an antiparallel double-stranded beta-helix for the XVMe major conformation in solution. An extensive set of distances (from NOE cross peaks) and H-bonds (from delta(NH)) has been included in the molecular dynamics calculations. The experimental NMR data and theoretical calculations clearly indicate that the most probable conformation of XVMe in solution is a double-strand antiparallel beta(5.6) increasing decreasing-helix structure.

Conformational and structural analysis of the equilibrium between single‐ and double‐strand β‐helix of a D,L‐alternating oligonorleucine

“…Both experimental NMR data and molecular dynamics calculations indicate that the main conformation for this peptide is a dimeric antiparallel ␤-helix structure ␤ 5. 6 12. The observation of some NOEs correlations HN(i)-␣H(iϩ4) and the H-bonds network by ␦ HN and temperature coefficient values suggest a single ␤-helix structure ␤ 4.4 for the second conformation.…”

“…In RMD calculations at 500 K, we found that the experimental restraints are only compatible with the model ␤ 5. 6 12, and that the calculation results are independent of the initial coordinates, as proved by the RMSD and energy values shown in Table V In order to analyze the dimer-monomer equilibrium, the effect of temperature was studied. The results obtained from the measurements at ten different temperatures fit well with the second-order Van't Hoff equation, as it is shown in Figure 5.…”

“…(2) the K d value is calculated. When ln K d vs 1/T is represented (Figure 6b) the equation for the regression analysis is ln K d ϭ 3.01ϫ10 6 1/T 2 Ϫ 25396.1 1/T ϩ 47.86 with a regression coefficient r 2 ϭ 0.99. The characterization of the ⌬G dependence with respect to the temperature can be calculated by Eq.…”

“…Noteworthy, in spite of the differences in the N-terminal group and the main-chain length, this conformation is identical to the one adopted by the oligopetide Boc-XVMe-OMe in chloroform solution. 6 Simulated annealing calculations were carried out as alternative method to verify the folding of the HCO-XMe-OMe dimer conformation, using as initial coordinates two antiparallel strands in an extended conformation, as described above. The most relaxed structures from a SARMD, using exclusively distance constraints from NMR data, show a distortion at the termini of the double helix, with a total average energy of Ϫ105.10kcal/mol and RMSD values of 1.50 and 3.22 Å from ␤…”

“…3 In our previous work, the structure of two D,L alternating oligonorleucines with Boc-(tert-butyloxycarbonyl) and MeO-end groups has been determined. 5,6 One-dimensional (1D) and two-dimensional (2D) NMR data for Boc-XIIMe-OMe oligopeptide clearly point to a simple right-handed ␤ 4.4 -helix conformation in chloroform. 5 This global structure is supported by the observation of nuclear Overhauser effect (NOE) cross peaks between HN(i)-␣H(iϩ4) for odd residues and HN(i)-␣H(iϪ4) for even residues, and H-bond network deduced from ␦ HN values.…”