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Acetolactate synthase (ALS) catalyzes the first common reaction in the biosynthesis of branched-chain amino acids, valine,leucine, and isoleucine ALS is the common target of several classes of structurally diverse herbicides, the triazolopyrimidines, the imidazolinones, the sulfonylureas, and pyrimidyl-oxy-benzoates. We examined ihibitory activities of newly synthesized triazolopyrimidine sulfonamide derivatives using partially purified ALS from barley IC50 values for the active derivatives are O.5nN∼8μM. Among them TP1 and TP2 are the most potent ALS inhibitors with IC50 values of 0.5nM and 1.6nM,respectively. These inhibitors are more potent in the inhibition of barley ALS than commercial herbicides,Metosulam (IC50;3.6nM), Flumetsulam (IC50;126nM), and Cadre (IC50;4 μM). The progress curves for inhibition of ALS by TP2 showed that the amount of inhibition increases with time. The inhibition of ALS by TP2 was mixed-type inhibition with respect to pyruvate Dual inhibition analyses of TP2 versus an imidazolinone, Cadre, and Leu showed parallel and intercepting kinetic pattern, respectively. The results suggest that TP2 binds to ALS competively with Cadre but not with Leu.Chemical modification of cysteinly residues in ALS decreased the sensitivity of ALS to Leu, while the modification did not affect the sensitivity of ALS to TP2 and Cadre.
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