Studies on thiamine diphosphate-dependent enzymes.

نویسندگان

  • F J Leeper
  • D Hawksley
  • S Mann
  • C Perez Melero
  • M D H Wood
چکیده

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 E1 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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عنوان ژورنال:
  • Biochemical Society transactions

دوره 33 Pt 4  شماره 

صفحات  -

تاریخ انتشار 2005