FARNESOL OXIDATION IN INSECTS--CHARACTERIZATION

描述（来自申请人的摘要）：保幼激素（JH）是 一种结构独特的倍半萜类化合物，仅在无脊椎动物中发现， 一些植物。因为已经确定精确调节JH水平 是调节昆虫生长发育所必需的，抑制JH 生物合成可以被看作是一种选择性杀死 昆虫事实上，阻断JH生物合成的化合物（称为抗juvenoids） 是已知的，并且有几个具有商业重要性。 该提案概述了旨在了解一个必要步骤的实验， 昆虫保幼激素的生物合成，即法尼醇氧化成 法尼萨尔对负责的酶（或酶）知之甚少。 金合欢醇在昆虫中的代谢;然而，先前的研究表明， 高度底物特异性的过程，可以由氧化酶催化，而不是 而不是脱氢酶 为了更好地表征昆虫中法尼醇的代谢， 为了确保抗juvenoid开发的适用性，我们将执行以下操作 实验：i）我们将合成和测试各种法尼醇类似物， 确定活动所需的结构参数，ii）我们将 确定是否有一种以上的酶参与JH的产生， 特别是因为它涉及JH同系物生物合成，iii）我们将确定 哪类氧化酶参与法尼醇代谢，iv）我们将 尝试使用传统的色谱法将酶纯化至均匀 方法，以及v）我们将合成和测试一系列化合物作为潜在的 昆虫中法尼醇（和JH）代谢的选择性抑制剂。 从这些研究中获得的信息应该有助于更好地 了解JH代谢，并可能有助于开发替代药物 昆虫控制策略。

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.