Regioselectivity preference of testosterone hydroxylation by cytochrome P450 3A4

被引：0
作者：
Yan Zhang
Phani Morisetti
Jeffery Kim
Lynelle Smith
Hai Lin
机构：
[1] University of Colorado Denver,Chemistry Department
[2] Rush University Medical College,undefined
来源：
Theoretical Chemistry Accounts | 2008年 / 121卷
关键词：
Cytochrome P450 3A4; Testosterone hydroxylation; Regioselectivity; Density functional theory;
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摘要：
Theoretical studies are presented into the experimentally observed regioselectivity difference of testosterone hydroxylation by cytochrome P450 3A4 at the 1β, 2β, 6β, and 15β positions. Such regioselectivity is investigated by density functional theory calculations on a model system. The barrier heights of hydrogen abstraction, which are corrected by zero-point vibrational energies, are computed to be about 10.1, 13.6, 14.4, and 16.2 kcal/mol for the 6β-, 2β-, 15β-, and 1β-positions, respectively. The calculated barriers suggest the regioselectivity preference of 6β ≫ 2β > 15β > 1β, which is in good agreement with experimental findings.
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页码：313 / 319
页数：6
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