Abstract
Replacement of the thiazolium ring of thiamine pyrophosphate with a triazole gives extremely potent inhibitors of pyruvate decarboxylase from Z. mobilis, with K(I) values down to 20 pM; this system was used to explore pyrophosphate mimics and several effective analogues were discovered.
MeSH terms
-
Biomimetic Materials / chemical synthesis
-
Biomimetic Materials / pharmacology
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacology*
-
Kinetics
-
Pyruvate Decarboxylase / antagonists & inhibitors*
-
Pyruvate Decarboxylase / metabolism
-
Thiamine Pyrophosphate / analogs & derivatives*
-
Thiamine Pyrophosphate / chemical synthesis
-
Thiamine Pyrophosphate / pharmacology
-
Triazoles / chemical synthesis*
-
Triazoles / pharmacology*
-
Zymomonas / enzymology*
Substances
-
Enzyme Inhibitors
-
Triazoles
-
Pyruvate Decarboxylase
-
Thiamine Pyrophosphate