| Abstract
| - Although many nonpeptidic drugs target biological membrane and membrane proteins, it is still difficult todefine the membrane-bound structure of the drugs. In this study, we utilized bicelles as a membrane model,since the bicelles, which have planar lipid bilayer portions, are thought to be a more appropriate and practicalmembrane model than micelles. Bicelles with a small diameter allow for measurements of liquid NMR dueto fast tumbling in solution. We targeted erythromycin A (EA) as a membrane-binding compound becauseit is pointed out that the drug interacts with lysosomal membranes, inhibits phospholipase A, and consequentlyinduces phospholipidosis as a side effect. The conformation of EA in the bicelle was successfully determinedon the basis of coupling constants and NOEs. Measurements of intermolecular NOEs and paramagneticrelaxation times revealed that the drug is located shallowly in the membrane surface, with the dimethylaminogroup being close to the phosphate, and the macrolide portion adjacent to upper sides of the acyl chains.This study shows the general utility of isotropic bicelles for detailed conformational and orientational studiesof membrane-associated nonpeptidic drugs.
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