LIQUID-PHASE COMBINATORIAL SYNTHESIS

A concept termed liquid-phase combinatorial synthesis (LPCS) is descri bed, The central feature of this methodology is that it combines the a dvantages 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 wer e prepared, one of peptide and the second of nonpeptide origin, The pe ptide-based library was synthesized by a recursive deconvolution strat egy [Erb, E., Janda, K. D. and Brenner, S. (1994) Proc. Natl. Acad. Sc i. USA 91, 11422-11426] and several ligands were found within this lib rary to bind a monoclonal antibody elicited against mu-endorphin. The nonpeptide molecules synthesized were arylsulfonamides, a class of com pounds of known clinical bactericidal efficacy, The results indicate t hat the reaction scope of LPCS should be general, and its value to mul tiple, high-throughput screening assays could be of particular merit, since multimilligram quantities of each library member can readily be attained.