Biomolecular-chemical screening a novel screening approach for the discovery of biologically active secondary metabolites I. Screening strategy and validation

Chemical screening using thin-layer chromatography and various staining rea gents offers the opportunity to visualize an almost complete picture of a m icrobial secondary metabolite pattern (metabolic finger-print). A thorough application:of this strategy resulted in a number of biologically active ne w secondary metabolites, although the screening strategy is per se not corr elated to any biological activity. In the present paper we report on a nove l approach called biomolecular-chemical screening which combines the chemic al screening strategy with binding studies of biological relevance. Making: use of thin-layer chromatography (TLC) and subsequent staining, biomolecula r-chemical screening allows to examine binding properties of low molecular weight metabolites to certain bio-macromolecules. The screening strategy it self, as well as independent validation of the results using DNA as selecte d bio-macromolecule are presented. The biomolecular-chemical screening meth od is useful to screen binding behaviour towards DNA of both, pure metaboli tes by one-dimensional TLC, and crude extracts by two-dimensional TLC. Inve stigation of pure secondary metabolites as well as screening of crude micro bial extracts and new secondary metabolites obtained with this screening st rategy are presented in accompanying papers.