Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A: evidence from partition coefficients and molecular dynamics simulations.
The partition coefficient of cyclosporin A (CsA) was measured in octanol/water and heptane/water by centrifugal partition chromatography. By comparison with results from model compounds, it was deduced that the hydrogen-bonding capacity of CsA changed dramatically from an apolar solvent (where it is internally H-bonded) to polar solvents (where it exposes its H-bonding groups to the solvent). Molecular dynamics simulations in water and CCl4 support the suggestion that CsA undergoes a solvent-dependent conformational changes and that the interconversion process is slow on the molecular dynamics time scale.
el Tayar
N
N
Institut de Chimie Thérapeutique, Ecole de Pharmacie, Université de Lausanne, Switzerland.
Mark
A E
AE
Vallat
P
P
Brunne
R M
RM
Testa
B
B
van Gunsteren
W F
WF
D000591:Amino Acid Isomerases / Q000378:metabolism; D002251:Carbon Tetrachloride; D002352:Carrier Proteins / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002845:Chromatography; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016572:Cyclosporine / Q000737:chemistry*; D006536:Heptanes; D006860:Hydrogen Bonding; D008958:Models, Molecular; D000442:Octanols; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D012997:Solvents
D002352:Carrier Proteins; D006536:Heptanes; D000442:Octanols; D012997:Solvents; D016572:Cyclosporine; D002251:Carbon Tetrachloride; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase