A new combination of protecting groups and links for encoded synthetic libraries suited for consecutive tests on the solid phase and in solution.
A strategy for high-throughput evaluation of combinatorial compound libraries is reported, which circumvents the necessity to test complex mixtures. The method is based on a new combination of protecting groups, solid-phase linker and tags. The bulk of the library first undergoes a binding assay with the components grafted on beads. A selection of beads carrying strong ligands is stripped from the labelled target and distributed into microvessels. The ligands are cleaved and rinsed into microeluates. Subsequently, a more detailed characterization with a functional assay in solution determines the best performers, which are identified through the peptidic tag left behind on the corresponding mother bead.
Felder
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ER
Pharmaceuticals Division, Ciba-Geigy AG, Basel, Switzerland.
Heizmann
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G
Matthews
I T
IT
Rink
H
H
Spieser
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E
D002625:Chemistry, Organic; D019020:Directed Molecular Evolution / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D055601:Organic Chemistry Phenomena; D019151:Peptide Library; D012996:Solutions; D013917:Thrombin / Q000037:antagonists & inhibitors
D008024:Ligands; D009842:Oligopeptides; D019151:Peptide Library; D012996:Solutions; D013917:Thrombin