BIOCHEMICAL APPROACHES TO HERBICIDE DISCOVERY - ADVANCES IN ENZYME TARGET IDENTIFICATION AND INHIBITOR DESIGN

This paper focuses primarily on the means by which biochemical informa tion can be used to identify enzymes which, upon inhibition, produce l ethal phenotypes and the enzyme inhibitor design strategies that have the highest probability of not only inhibiting the enzyme but also tra nslating that inhibition into herbicidal efficacy. The identification of an exquisitely lethal target site is the key initial component to t his approach and has often been one of the most difficult steps becaus e the attributes of a lethal site have, at best, been ill-defined. An examination of the characteristics of known targets provides some insi ght as to the definition of a lethal target. Recently, antisense RNA s uppression of enzyme translation has been used to determine the extent of inhibition required for toxicity and offers potential as a strateg y for identifying lethal target sites. After identification of a letha l target, detailed knowledge of the enzyme's chemical and kinetic mech anism as well as the protein's structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given en zyme. The advantages and disadvantages of a given type with respect to in vivo efficacy as well as the probability of herbicide resistance d evelopment will be discussed.