2-Oxo-3-alkynoic Acids, Universal Mechanism-Based Inactivators of Thiamin Diphosphate-Dependent Decarboxylases: Synthesis and Evidence for Potent Inactivation of the Pyruvate Dehydrogenase Multienzyme Complex†
1997
A new class of compounds, the 2-oxo-3-alkynoic acids with a phenyl substituent at carbon 4 was reported by the authors as potent irreversible and mechanism-based inhibitors of the thiamin diphosphate- (ThDP-) dependent enzyme pyruvate decarboxylase [Chiu, C.-F., & Jordan, F. (1994) J. Org. Chem. 59, 5763−5766]. The method has been successfully extended to the synthesis of the 4-, 5-, and 7-carbon aliphatic members of this family of compounds. These three compounds were then tested on three ThDP-dependent pyruvate decarboxylases: the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) and its E1 (ThDP-dependent) component, pyruvate oxidase (POX, phosphorylating; from Lactobacillus plantarum), and pyruvate decarboxylase (PDC) from Saccharomyces cerevisiae. All three enzymes were irreversibly inhibited by the new compounds. The 4-carbon acid is the best substrate-analog inactivator known to date for PDHc, more potent than either fluoropyruvate or bromopyruvate. The following conclusions were ...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
18
References
17
Citations
NaN
KQI