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Biochemical Approaches to Herbicide Discovery: Advances in Enzyme Target Identification and Inhibitor Design

Published online by Cambridge University Press:  12 June 2017

Lynn M. Abell
Lynn M. Abell*
Affiliation:
E. I. du Pont de Nemours, Agricultural Products, Stine-Haskell Research Center, Newark, DE 19714
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Abstract

This paper focuses primarily on the means by which biochemical information can be used to identify enzymes which, upon inhibition, produce lethal phenotypes and the enzyme inhibitor design strategies that have the highest probability of not only inhibiting the enzyme but also translating that inhibition into herbicidal efficacy. The identification of an exquisitely lethal target site is the key initial component to this approach and has often been one of the most difficult steps because the attributes of a lethal site have, at best, been ill-defined. An examination of the characteristics of known targets provides some insight as to the definition of a lethal target. Recently, antisense RNA suppression of enzyme translation has been used to determine the extent of inhibition required for toxicity and offers potential as a strategy for identifying lethal target sites. After identification of a lethal target, detailed knowledge of the enzyme's chemical and kinetic mechanism as well as the protein's structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. The advantages and disadvantages of a given type with respect to in vivo efficacy as well as the probability of herbicide resistance development will be discussed.

Keywords

ALS, acetolactate synthase or acetohydroxy acid synthase, E.C. 4.1.3.18GS, glutamine synthetase, E.C. 6.3.1.2EPSPS, 5-enolpyruvylshikimate-3-phosphate synthase, E.C.2.5.1.19KARI, ketol-acid reductoisomerase, E.C. 1.1.1.86IMI, α isopropyl malate isomerase, E.C. 4.2.1.33IPMDH, β isopropyl malate dehydrogenase, E.C. 1.1.1.85GSA-AT, glutamate-1-semialdehyde, E.C. 5.4.3.8TD, threonine deaminase, E.C.4.2.1.16ACCase, acetylCoA carboxylase, E.C.6.4.1.2IGPD, imidazole glycerol phosphate dehydratase, E.C.4.2.1.19PEP, phosphoenolpyruvateIpOHA, [N-isopropyl oxalyl hydroxamate]Hoe 704 [2-dimethyl-phosphinoyl-2-hydroxyacetic acid]PQ, plastoquinonephosphinothricin, (glufosinate) [2-amino-4-(hydroxymethylphosphinyl)butanoic acid]glyphosate, [N-(phosphonomethyl)glycine]gabaculine, [5-amino-l,3-cyclohexadienyl carboxylate]Antisensereaction intermediate analoguesextraneous site inhibitors
Type
Symposium
Information
Weed Science , Volume 44 , Issue 3 , September 1996 , pp. 734 - 742
Copyright
Copyright © 1996 by the Weed Science Society of America 

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References

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