Anesthetic steroid mobility in model membrane preparations as examined by high-resolution 1H and 2H NMR spectroscopy.
A series of structurally related pregnane analogues which exhibit a wide range of anesthetic potencies were incorporated into unilamellar egg lecithin vesicles and their relative mobilities examined with 1H and 2H high-resolution NMR spectroscopy. The data from this study reveal a trend suggesting a relationship between the motional properties of a steroid and its anesthetic potency. The data are congruent with the idea that anesthetic activity is associated with perturbation of the membrane bilayer by the steroid molecule; the degree to which the membrane is perturbed is apparently dependent upon the specific structural and stereochemical features of the steroid. This study supports the hypothesis that lipid bilayers are capable of a high degree of structural discrimination.
Makriyannis
A
A
School of Pharmacy, University of Connecticut, Storrs 06268.
DiMeglio
C M
CM
Fesik
S W
SW
D000777:Anesthetics / Q000138:chemical synthesis* / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011278:Pregnanes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000777:Anesthetics; D008051:Lipid Bilayers; D011278:Pregnanes