Synthesis and evaluation of substrate analogues as mechanism-based inhibitors of type II isopentenyl diphosphate isomerase.
J Org Chem
; 73(2): 726-9, 2008 Jan 18.
Article
in En
| MEDLINE
| ID: mdl-18088143
ABSTRACT
Type 2 isopentenyl diphosphate isomerase (IDI-2), which catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, contains a tightly bound molecule of FMN. To probe the mechanism of the reaction, cyclopropyl and epoxy substrate analogues, designed to be mechanism-based irreversible inhibitors, were synthesized and evaluated with IDI-2 from Thermus thermophilus. The cyclopropyl analogues were alternative substrates. The epoxy analogue was an irreversible inhibitor, with kI = 0.37 +/- 0.07 min(-1) and KI = 1.4 +/- 0.3 microM. LC-MS studies revealed formation of an epoxide-FMN adduct.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbon-Carbon Double Bond Isomerases
/
Cyclopropanes
/
Epoxy Compounds
Language:
En
Journal:
J Org Chem
Year:
2008
Document type:
Article