Studies on thiamine diphosphate-dependent enzymes

被引：17

作者：

Leeper, FJ ^{[1
]}

Hawksley, D ^{[1
]}

Mann, S ^{[1
]}

Melero, CP ^{[1
]}

Wood, MDH ^{[1
]}

机构：

[1] Univ Cambridge, Chem Lab, Cambridge CB2 1EW, England

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2005年 / 33卷

关键词：

deazathiamine diphosphate (deazaTPP); Friedel-Crafts acylation reaction; thiazolium ring; V-conformation; ylid;

D O I：

10.1042/BST0330772

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 3-deaza analogue of TPP (thiamine diphosphate), a close mimic of the ylid intermediate, has been synthesized and is an extremely potent inhibitor of a variety of TPP-dependent enzymes, binding much more tightly than TPP itself. Results using deazaTPP complexed with the El subunit of PDH (pyruvate dehydrogenase) have led to a novel proposal about the mechanism of this enzyme. The 2-substituted forms of deazaTPP, which mimic other intermediates in the catalytic mechanism, can also be synthesized and 2-(1-hydroxyethyl)deazaTPP is also an extremely potent inhibitor of PDC (pyruvate decarboxylase). Attachment of such 2-substituents is expected to be a way to introduce selectivity in the inhibition of various TPP-dependent enzymes.

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页码：772 / 775

页数：4

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