Abstract |
Acetolactate Synthase(ALS)는 가지를 가진 아미노산 valine, leucine, isoleucine의 생합성 과정에서 공통적으로 작용하는 효소이다. ALS는 서로 구조적 유사성이 없는 최근에 개발된 sulfonylurea, imidazolinone, 그리고 triazolopyrimidine계 제초제들의 공통적인 작용표적이다. 완두로부터 분리한 ALS 를 이용하여 새로 합성한 4,6-dimethoxypyrimidine 유도체들의 저해활성을 측정하였다. 가장 우수한 저해활성을 나타내는 유도체는 K11570으로 IC50값이 0.2μM이다. 완두의 ALS에 대한 K11570의 저해활성은 incubation 시간이 증가함에 따라 증가하였으며, 기질 pyruvate에 대해 혼합형 저해유형을 보여주었다. K11570와 sulfonylurea Ally, 그리고 feedback 저해제 leucine에 대한 dual inhibition 실험결과 이들 저해제의 결합부위가 최소한 부분적으로 겹치는 것으로 생각된다. Arg을 변형시킨 효소는 K11570, sulfonylurea Ally, 그리고 leucine의 저해 민감도의 변화가 관찰되었으나ㅑ, Trp의 변형은 저해 민감도에 영향이 없었다. Acetolactate synthase(ALS) is the common enzyme in the biosynthetic of valine, leucine, and isoleucine, and is the target of several classes of structually unrelated herbicides, including sulfonylureas, imidazolinones, and triazolopyrimidines. In an effort to develop new and desirable herbicides, we have synthesized 4,6-dimethoxypyrimidine derivatives, and examined their inhibitory activities on pea ALS. The most active compound was found to be K11570 and IC50 value for K11570 was 0.2 μM. The inhibition of pea ALS by K11570 was biphasic, showing increased inhibition with incubation time. The K11570 showed mixed-type inhibition with respect to substrate pyruvate. Dual inhibition analysis of K11570 versus sulfonylurea herbicide Ally and feedback inhibitor leucine revealed that three inhibitors were competitive for binding to ALS. The arginine modified enzyme showed decreased inhibition by K11570, sulfonylurea Ally, and leucine, in constrast to, tryptophan modification did not affect on the sensitivity of ALS to the inhibitors. |
