Arylhydroxamic acid bioactivation via acyl group transfer. Structural requirements for transacylating and electrophile-generating activity of N-(2-fluorenyl)hydroxamic acids and related compounds.
Arylhydroxamic acid bioactivation via acyl group transfer. Structural requirements for transacylating and electrophile-generating activity of N-(2-fluorenyl)hydroxamic acids and related compounds.
复制标题
芳基异羟肟酸通过酰基转移进行生物活化。
DOI：
10.1021/jm00349a015
复制
发表时间：
1982
影响因子：
7.3
通讯作者：
P. E. Hanna
中科院分区：
文献类型：
--
作者：
H. Yeh;P. E. Hanna
合成了12个N-(2-荧基)-N-羟基甲酸酯、N-(2-荧基)-N-羟基脲和N-(2-荧基)-N-羟氨基甲酸酯。评估了这些化合物作为部分纯化的地鼠肝脏芳基异羟肟酸N，O-酰基转移酶制剂的底物的能力。以4-氨基偶氮苯为酰基受体，用分光光度法测定转酰化活性，用N-乙酰蛋氨酸捕捉法测定产物的凝胶生成活性。只有N-乙酰基、N-丙酰基和N-甲氧基乙酰基衍生物表现出相对较高的活性。这些结果与以前报道的关于该酶系统激活所需的酰基的空间和电子特性的结论基本一致。N-羟基-2-乙酰氨基荧灭活N，O-乙酰基转移酶对N-乙酰基化合物生物活性的抑制作用大于N-丙酰基或N-甲氧基乙酰基衍生物。
The synthesis of a series of 12 N-(2-fluorenyl)hydroxamic acids, N-(2-fluorenyl)-N-hydroxyureas, and N-(2-fluorenyl)-N-hydroxycarbamates is reported. The compounds were evaluated for their ability to serve as substrates for a partially purified hamster hepatic arylhydroxamic acid N,O-acyltransferase preparation. Transacylating activity was measured spectrophotometrically with 4-aminoazobenzene as the acyl group acceptor, and electrophile-generating activity was quantified by the N-acetylmethionine trapping assay. Only the N-acetyl, N-propionyl, and N-methoxyacetyl derivatives exhibited relatively high levels of activity as measured by either of the assay methods. These results are generally consistent with previously reported conclusions regarding the steric and electronic characteristics of acyl groups that are required for activation by this enzyme system. N,O-Acyltransferase inactivation by N-hydroxy-2-acetamidofluorene depressed the bioactivation of the N-acetyl compound to a greater extent than either the N-propionyl or N-methyloxyacetyl derivative.