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Drug discovery from Nature automated high-quality sample preparation.pdf

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Drug discovery from Nature automated high-quality sample preparation

Drug discovery from Nature: automated high-quality sample preparation Ralf Thiericke Hans-K no?ll-Institute f or N atural Products Research, Beutenberg stra?e 11, D- 07745, J ena, Germany. e-mail: thierick@pmail.hki-jena.de Secondary metabolites f rom plants, animals and microorganisms have been proven to be an outstanding source for new and innovative drugs and show a striking structural diversity that supplements chemically synthesized compounds or libraries in drug discovery prog rams. Unf ortunately, extracts from natural sources are usually complex mixtures of compounds: of ten generated in time consuming and for the most part manual processes. As quality and quantity of the provided samples play a pivotal role in the success of high-throughput screening programs this poses serious problems. In order to make samples of natural orig in competitive with synthetic compound libraries, we devised a novel, automated sample preparation procedure based on solid-phase extraction (SPE ) . By making use of a modi?ed Zymark RapidT race1 SPE workstation an easy-to-handle and e ? ective f ractionation method has been developed which allows the generation of high- quality samples f rom natural orig in, ful? lling the requirements of an integration into high-throughput screening programs. Introduction Concepts to improve the generation and identi? cation of lead structures are key issues in the development of new pharmaceuticals and agro-chemicals. In the early stages of drug discovery high sample numbers are requested to feed the current capacities of the high-throughput screen- ing (HTS) machinery. At present, compound libraries from combinatorial chemistry are the major source for HTS programs. On the other hand, however, nature has been proven to be an outstanding source for new and innovative drugs [1]. Numerous examples from medicine, such as cyclosporin A, lovastatin, acarbose, paclitaxel, FK506, topotecan, or miglitol, impressively demonstrate the innovative potential