MODELS FOR THE BINDING OF AMIODARONE TO THE THYROID-HORMONE RECEPTOR

被引：13

作者：

CHALMERS, DK ^{[1
]}

MUNRO, SLA ^{[1
]}

ISKANDER, MN ^{[1
]}

CRAIK, DJ ^{[1
]}

机构：

[1] VICTORIAN COLL PHARM,SCH PHARMACEUT CHEM,381 ROYAL PARADE,PARKVILLE,VIC 3052,AUSTRALIA

来源：

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN | 1992年 / 6卷 / 01期

关键词：

MOLECULAR GRAPHICS; CONFORMATIONAL SEARCH; MOLECULAR MECHANICS; SEMIEMPIRICAL MOLECULAR ORBITAL CALCULATIONS;

D O I：

10.1007/BF00124384

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The antiarrhythmic drug amiodarone has recently been characterized as the first known thyroid hormone antagonist. Its mode of interaction with the thyroid hormone receptor is therefore of interest. A computational analysis of the conformational flexibility of amiodarone using molecular mechanics and the semiempirical molecular orbital method AM1 has been performed. The molecular mechanics studies show that the low-energy conformations of the benzoylbenzofuran portion of amiodarone can be grouped into 4 distinct classes, while the diethylaminoethoxy side chain is extremely flexible. Conformers representative of the 4 low-energy classes were fitted to an extended thyroid hormone receptor model. Four independent modes in which amiodarone could bind to the thyroid hormone receptor site were evaluated.

引用

页码：19 / 31

页数：13

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