Arthropod-Based Libraries for High Throughput Screening

描述（由申请人提供）：在过去的四十年里，我们一直在研究陆生昆虫和其他节肢动物之间的防御和交流化学，这是一组生物，包括地球上所有已描述物种的一半以上。虽然我们所鉴定的许多化合物结构简单（如直链烯烃、羧酸、醛类、酚类、苯醌类），但我们在研究过程中也发现了许多具有生物活性的生物碱、类异戊二烯（包括类固醇）和具有新结构的多肽。我们计划选择大约10个最有趣的结构，并准备由天然产物本身加上-5-30个相关结构组成的中试规模文库，其数量适合高通量筛选。从药物发现的角度来看，这个项目是我们在天然产物化学领域多年研究的高潮。Ds和建议的衍生物通常代表尚未通过高通量筛选检查的分子结构。在这些文库中发现与神经药理学、传染病和寄生虫病或癌症等领域相关的活动的可能性远远大于对化学空间的其他领域进行研究的可能性，这些领域不是基于生物来源的小分子。

DESCRIPTION (provided by applicant): Over the past four decades, we have been studying the chemistry of defense and communication among terrestrial insects and other arthropods, a group of organisms that includes over half of all described species on earth. While many of the compounds we have characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and polypeptides with novel structures which we have discovered in the course of this research. We plan to select approximately ten of the most interesting structures and to prepare pilot-scale libraries consisting of the natural product itself plus -5-30 related structures in quantities suitable for high throughput screening. This project is the culmination, from the viewpoint of drug discovery, of our many years of research in the field of natural products chemistry. ds and proposed derivatives generally represent molecular structures that have not yet been examined via high throughput screening. The likelihood of discovering activities within these libraries of relevance to areas such as neuron-pharmacology, infectious and parasitic diseases, or cancer is much greater than would be expected from a study of other areas of chemical space which are not based on small molecules of biological origin.