Chemistry of Arthropod Secretions

描述(申请人提供)：昆虫和其他陆生节肢动物占地球上所有描述物种的一半以上。虽然这些物种中的大多数对人类生活没有立竿见影的影响，但有些作为疾病媒介(如采采蝇、按蚊、三叶虫、扁虱等)极其重要，有些已经发展成为农业、森林和家庭害虫。此外，蜘蛛及其近亲具有特殊的药理价值，因为它们能够合成能够麻痹猎物的毒液。化学物质在节肢动物的生活中起着核心作用。这个项目的目的是阐明节肢动物的化学，基于关键的生物进化考虑，以应该导致改善人类健康和福利的方式。 在我们的实验方法中，我们计划开发利用核磁共振波谱对从节肢动物来源获得的生物活性样本进行初步研究。随着核磁共振光谱仪的灵敏度不断提高，以及多维分析技术的非凡能力，现在即使对蜘蛛毒液或昆虫全身提取物中发现的复杂混合物进行有用的核磁共振分析也是现实的。具体地说，我们的计划包括在蜘蛛和蝎子的毒液中寻找新的神经毒素；合成新发现的毒液成分用于生物筛选；表征一种捕食者产生的抑制蚊子产卵的凯洛酮；从昆虫幼虫和蛹中寻找新的杀虫药物；从萤火虫中阐明新的强心剂的结构。我们的总体目标是(1)发现重要的节肢动物相互作用的化学基础，(2)为适用于病媒生物的新的控制技术提供基础，以及(3)从节肢动物来源中寻找新的生物活性化学类型，这些类型可以作为药物开发或媒介控制的先导化合物。

DESCRIPTION (provided by applicant): Insects and other terrestrial arthropods make up over half of all described species on earth. Although the majority of these species have no immediate impact on human life, some are extremely important as disease vectors (i.e. tsetse fly, anopeheline mosquitoes, triatomine bugs, ticks ...), and some have developed into agricultural, forest, and household pests. In addition, spiders and their relatives are of particular pharmacological interest because of their ability to synthesize venoms capable of paralyzing their prey. Chemistry plays a central role in the lives of arthropods. The aim of this project is to elucidate arthropod chemistry based on critical, biorational considerations, in ways that should lead to the improvement of human health and welfare. In our experimental approach, we plan on developing the use of NMR spectroscopy for the initial study of bioactive samples obtained from arthropod sources. With the ever-increasing sensitivity of NMR spectrometers, and the remarkable power of multidimensional analytical techniques, it is now realistic to carry out useful NMR analyses even on complex mixtures such as those found in spider venoms, or in whole-insect-body extracts. Specifically, our plans include the search for novel neurotoxins in the venoms of spiders and scorpions; the synthesis of newly-discovered venom components for biological screening; the characterization of a predator-produced kairomone which inhibits mosquito oviposition; a search for new anti-insect agents from insect larvae and pupae; elucidation of the structures of new cardiotonic agents from fireflies. Our overall objectives are (1) to discover the chemical basis for important arthropod interactions, (2) to provide the basis for new control techniques applicable to disease vectors, and (3) to find from arthropod sources new biologically active chemotypes which may serve as lead compounds in drug development or vector control.