Arthropod-Based Libraries for High Throughput Screening

描述（由申请人提供）：在过去的四十年里，我们一直在研究陆地昆虫和其他节肢动物之间的防御和通信化学，这是一组包括地球上所有描述物种一半以上的生物体。 虽然我们所表征的许多化合物具有简单的结构（如直链烯烃、羧酸、醛、酚、苯醌），但也有许多生物活性生物碱、类异戊二烯（包括类固醇）和具有新结构的多肽的例子，我们在本研究过程中发现了这些例子。 我们计划选择大约10个最感兴趣的结构，并制备中试规模的文库，该文库由天然产物本身加上适于高通量筛选的量的约5 - 30个相关结构组成。 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成果。 DS和提出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，远远大于对不基于生物来源小分子的化学空间其他领域进行研究所预期的可能性。

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.