Bioactive peptides: Solid state, solution and molecular dynamics studies of a cyclolinopeptide A-related cystinyl cyclopentapeptide

The conformational analysis of the disulphide cyclopeptide‐related cyclolinopeptide A, has been carried out by solid state methods using x‐ray diffraction techniques, in solution by nmr, CD, ir spectroscopies, and by molecular dynamics (MD) analysis. The structure of the monoclinic form, obtained from ethanol (a = 11.303(2) Å, b = 14.467(8) Å, c = 12.355(2) Å, β(°) = 109.40(1), space group P21, Z = 2) presents two transannular H bonds with the formation of one type VIa β‐turn involving the C  O of the urethane moiety and the Phe3 NH, and an intramolecular H bond between the C  O of urethane group and the Phe4 NH. In the solid state all the peptide bonds are in the trans configuration with the exception of a cis peptide bond occurring between the Cys1 and Pro2 residues; the linkage S—S assumes right‐handed chirality. The conformational study in solution by nmr spectroscopy indicates that the peptide is very flexible and that some conformer families are present at room temperature both in polar and apolar solvents. CD studies confirm that this cyclic system tends to give rise to a complex mixture of quasi‐isoenergetic conformations, favored by the flexibility of the disulphide bridge and by the isomerism of the Xxx‐Pro bond. MD studies carried out in vacuo and in solution shows that the structure determined by solid state represents a energy minimum. All hydrogen conds found in the crystalline state are correctly reproduced in vacuo and in solution simulations. © 1994 John Wiley & Sons, Inc.