ONE-BEAD ONE-STRUCTURE COMBINATORIAL LIBRARIES

Combinatorial libraries employing the one-bead-one-compound technique are reviewed, Two distinguishing features characterize this technique. First, each conmpound is identified with a unique solid support, enab ling facile segregation of active compounds. Second, the identity of a compound on a positively reacting bead is elucidated only after its b iological relevance is established. Direct methods of structure identi fication (Edman degradation and mass spectroscopy) as well as indirect ''coding'' methods facilitating the synthesis and screening of nonpep tide libraries are discussed. Nonpeptide and ''Scaffold'' libraries. t ogether with a new approach for the discovery of a peptide binding mot if using a ''library of libraries,'' are also discussed. In addition, the ability to use combinatorial libraries to optimize initially disco vered leads is illustrated with examples using peptide libraries. (C) 1995 John Wiley & Sons, Inc.