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Solution conformations of cyclosporins and magnesium‐cyclosporin complexes determined by vibrational circular dichroism
Author(s) -
Bodack Louise A.,
Freedman Teresa B.,
Chowdhry Babur Z.,
Nafie Laurence A.
Publication year - 2003
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.10513
Subject(s) - chemistry , hydrogen bond , conformational isomerism , crystallography , cyclosporins , magnesium , infrared spectroscopy , vibrational circular dichroism , circular dichroism , amide , stereochemistry , molecule , computational chemistry , organic chemistry , medicine , surgery , transplantation
Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl 3 , in the amide I and NH/OH‐stretching regions, and their corresponding magnesium complexes in CD 3 CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of CO and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6‐31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl 3 solution; CsH, however, assumes both an intramolecularly hydrogen‐bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH‐stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen‐bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal‐free and magnesium‐complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 163–177, 2004