Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-val-Leu-) An NMR spectroscopy and molecular modeling study |
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Authors: | NINA C GONNELLA XIAOLU ZHANG YONG JIN OM PRAKASH C GREGORY PARIS ISTVAN KOLOSSVRY WAYNE C GUIDA REGINE S BOHACEK ISIDOROS VLATTAS TERRI SYTWU |
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Institution: | NINA C. GONNELLA,XIAOLU ZHANG,YONG JIN,OM PRAKASH,C. GREGORY PARIS,ISTVAN KOLOSSVÁRY,WAYNE C. GUIDA,REGINE S. BOHACEK,ISIDOROS VLATTAS,TERRI SYTWU |
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Abstract: | The conformations of cyclo(-D-Trp-D-Asp-Pro-D-val-Leu-) in dimethyl sulfoxide-d6 (DMSO-d6) and water were determined using two-dimensional nuclear magnetic resonance spectroscopy and restrained molecular dynamics. Comparisons were made between conformations of the cyclic pentapeptide in both solvents. The NMR study revealed that, while the backbone remained relatively unchanged in both solvents, the side-chains adopted distinctly different orientations in DMSO-d6 vs. H2O. A modeling study, minus NOE constraints, produced a set of low-energy conformers possessing agreement in backbone conformation with the NMR-derived structures; however, lowest-energy conformers did not have this agreement. These results show that different solvents can significantly affect the preferred side-chain conformation of small cyclic peptides in solution. This finding will impact the selection of solvent when determining structures for use as templates in rational drug design. |
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Keywords: | cyclic pentapeptide 1 H NMR spectroscopy 2D NOE NMR spectroscopy restrained molecular dynamics selective endothelin-A receptor antagonist |
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