Detailed description of the conformation and location of membrane-bound erythromycin A using isotropic bicelles

Nobuaki Matsumori, Atsushi Morooka, Michio Murata

研究成果: ジャーナルへの寄稿学術誌査読

21 被引用数 (Scopus)

抄録

Although many nonpeptidic drugs target biological membrane and membrane proteins, it is still difficult to define 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 practical membrane model than micelles. Bicelles with a small diameter allow for measurements of liquid NMR due to fast tumbling in solution. We targeted erythromycin A (EA) as a membrane-binding compound because it is pointed out that the drug interacts with lysosomal membranes, inhibits phospholipase A, and consequently induces phospholipidosis as a side effect. The conformation of EA in the bicelle was successfully determined on the basis of coupling constants and NOEs. Measurements of intermolecular NOEs and paramagnetic relaxation times revealed that the drug is located shallowly in the membrane surface, with the dimethylamino group 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 studies of membrane-associated nonpeptidic drugs.

本文言語英語
ページ(範囲)3501-3508
ページ数8
ジャーナルJournal of Medicinal Chemistry
49
12
DOI
出版ステータス出版済み - 6月 15 2006
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 創薬

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