FARNESOL OXIDATION IN INSECTS--CHARACTERIZATION

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DESCRIPTION (verbatim from the applicant's abstract): Juvenile hormone (JH) is a structurally unique sesquiterpenoid found exclusively in invertebrates and some plants. Since it is well established that precise modulation of JH levels is required for regulating insect growth and development, inhibition of JH biosynthesis can be viewed as a potential method for selectively killing insects. Indeed, compounds that block JH biosynthesis (termed anti-juvenoids) are known and several are of commercial importance. This proposal outlines experiments aimed at understanding a required step in insect juvenile hormone biosynthesis, namely the oxidation of farnesol to farnesal. Very little is known about the enzyme (or enzymes) responsible for farnesol metabolism in insects; however, prior studies indicate that it is a highly substrate-specific process that may be catalyzed by an oxidase, rather than a dehydrogenase. To better characterize farnesol metabolism in insects and to ascertain its suitability for anti-juvenoid development, we will perform the following experiments: i) we will synthesize and test a variety of farnesol analogs, to determine the structural parameters required for activity, ii) we will determine whether more than one enzyme is involved in JH production, specifically as it relates to JH homolog biosynthesis, iii) we will determine what class of oxidative enzyme is involved in farnesol metabolism, iv) we will attempt to purify the enzyme to homogeneity, using traditional chromatographic methods, and v) we will synthesize and test a series of compounds as potential selective inhibitors of farnesol (and JH) metabolism in insects. The information obtained from these studies should be useful in better understanding JH metabolism and may be useful in developing alternative strategies for insect control.