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Bioactive peptides: Solid state, solution and molecular dynamics studies of a cyclolinopeptide A‐related cystinyl cyclopentapeptide
Author(s) -
Rossi Filomena,
Saviano Michele,
Di Blasio Benedetto,
Zanotti Giancarlo,
Maione Anna Maria,
Tancredi Teodorico,
Pedone Carlo
Publication year - 1994
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360340213
Subject(s) - chemistry , conformational isomerism , intramolecular force , moiety , hydrogen bond , crystallography , monoclinic crystal system , peptide bond , chirality (physics) , nuclear magnetic resonance spectroscopy , solid state nuclear magnetic resonance , solid state , peptide , stereochemistry , molecule , crystal structure , organic chemistry , biochemistry , nambu–jona lasinio model , chiral symmetry breaking , physics , nuclear magnetic resonance , quantum mechanics , quark
The conformational analysis ofthe 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 P2 1 , 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 Phe 3 NH, and an intramolecular H bond between the C O of urethane group and the Phe 4 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 Cys 1 and Pro 2 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.