Synthesis of analogues of 5-aminolaevulinic acid and inhibition of 5-aminolaevulinic acid dehydratase

被引:17
作者
Appleton, D
Duguid, AB
Lee, SK
Ha, YJ
Ha, HJ
Leeper, FJ
机构
[1] Univ Cambridge, Cambridge Ctr Mol Recognit, Chem Lab, Cambridge CB2 1EW, England
[2] Hankuk Univ Foreign Studies, Dept Chem, Yongin Gun 449791, South Korea
来源
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1998年 / 01期
关键词
D O I
10.1039/a704544a
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Syntheses are described of several analogues of ti-aminolaevulinic acid (ALA), which are potential inhibitors of ALG dehydratase (porphobilinogen synthase), an early enzyme of tetrapyrrole biosynthesis. Most of the analogues are relatively weak competitive inhibitors of the enzyme from Bacillus subtilis or irreversible inhibitors due to multiple alkylation of the enzyme but the 3-oxa and 3-thia analogues are potent mechanism-based inhibitors which inactivate, by acylation of a nucleophilic residue, probably the active-site lysine residue. The kinetics of the inactivation by 3-thiaALA have implications for the mechanism of the enzymic reaction.
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页码:89 / 101
页数:13
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