Inhibition of Barley Acetolactate Synthase by Triazolopyrimidine Derivative

트리아졸로피리미딘계 유도체에 의한 보리 Acetolactate Synthase의 저해

  • Kim, Sung Ho (Department of Biochemistry, Chungbuk National University) ;
  • NamGoong, Sung Keon (Department of Chemistry, Seoul Womans University) ;
  • Shin, Jung Hyu (Department of Chemistry, Seoul National University) ;
  • Chang, Soo Ik (Department of Biochemistry, Chungbuk National University) ;
  • Choi, Jung Do (Department of Biochemistry, Chungbuk National University)
  • Published : 19990800

Abstract

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. $IC_{50}$ values for the active derivatives are 0.5nM∼8$\mu$M. Among them TP1 and TP2 are the most potent ALS inhibitors with $IC_{50}$ values of 0.5nM and 1.6nM, respectively. These inhibitors are more potent in the inhibition of barley ALS than commercial herbicides, Metosulam ($IC_{50}$;3.6 nM), Flumetsulam ($IC_{50}$;126 nM), and Cadre ($IC_{50};4 {\mu}M$). 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.

Keywords

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