LIQUID-PHASE COMBINATORIAL SYNTHESIS

A concept termed liquid-phase combinatorial synthesis (LPCS) is described, The central feature of this methodology is that it combines the advantages that classic organic synthesis in solution offers with those that solid-phase synthesis can provide, through the application of a linear homogeneous polymer. To validate this concept two libraries were prepared, one of peptide and the second of nonpeptide origin, The peptide-based library was synthesized by a recursive deconvolution strategy [Erb, E., Janda, K. D. and Brenner, S. (1994) Proc. Natl. Acad. Sci. USA 91, 11422-11426] and several ligands were found within this library to bind a monoclonal antibody elicited against mu-endorphin. The nonpeptide molecules synthesized were arylsulfonamides, a class of compounds of known clinical bactericidal efficacy, The results indicate that the reaction scope of LPCS should be general, and its value to multiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.