Proceedings of the National Academy of Sciences · 1995 · 156 citations · 16 references
PharmacyImmunologyMedicinal ChemistryCombinatorial ChemistryDrug DiscoveryMonoclonal AntibodiesAntibody DiscoveryAntibody Library ConstructionCombinatorial Peptide SynthesisCombinatorial SynthesisPeptide ChemistrySolid-phase SynthesisBactericidal AgentsHigh-throughput Screening AssaysMonoclonal Antibody InteractionsMonoclonal Antibody RecognitionPeptide Library ConstructionPeptide Library DesignPeptide Library ScreeningPeptide Library 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. & 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 beta-endorphin. The non-peptide 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.
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Light-Directed, Spatially Addressable Parallel Chemical Synthesis
Stephen P. A. Fodor, Jill Read, Michael C. Pirrung et al. · Science · 1991 · 2.7K citations
A new type of synthetic peptide library for identifying ligand-binding activity
Kit S. Lam, Sydney E. Salmon, Evan M. Hersh et al. · Nature · 1991 · 1.8K citations