Triazole-Based Thiamine Analogues as Inhibitors of Thiamine Pyrophosphate-Dependent Enzymes: 1,3-Dicarboxylate for Metal Binding.

ABSTRACT: Thiamine 1 (vitamin B1) is essential for energy metabolism, and interruption of its utilization pathways is linked to various disease states. Thiamine pyrophosphate 2a (TPP, the bioactive form of 1) functions as a coenzyme of a variety of enzymes. To understand the role of vitamin B1 in these diseases, a chemical approach is to use coenzyme analogues to compete with TPP for the enzyme active site, which abolishes the coenzyme function. Exemplified by oxythiamine 3a and triazole hydroxamate 4, chemical probes require the coenzyme analogues to be membrane-permeable and of broad inhibitory activity to the enzyme family (rather than being too selective to particular TPP-dependent enzymes). In this study, using biochemical assays, we show that changing the hyd

SUBMITTER: Ho TCS 

PROVIDER: S-EPMC11483378 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature