Application of 'one-bead one-compound' combinatorial library methods in signal transduction research

Kit Lam, Thomas Sroka, Man Ling Chen, Yu Zhao, Qiang Lou, Jinzi Wu, Zhan Gong Zhao

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Using a 'split-synthesis' solid phase synthetic approach, bead libraries can be generated such -that each bead displays only one chemical entity. This 'one-bead one-compound' combinatorial library can then be assayed for specific biological properties using either a solid-phase on-bead binding or functional assay, or a releasable solution phase assay. Positive compound- beads can then be isolated for structure determination. Various assay systems to screen such a 'one-bead one-compound' library are described. We have used this combinatorial library method to discover peptides that bind to the cell surface immunoglobulins of murine lymphoma cells. Such peptides, when presented in an oligomeric form to a lymphoma cell are able to induce signal transduction. Additionally, we have also applied the 'one-bead one-compound' combinatory library approach to elucidate peptide substrate motifs for protein tyrosine kinases. Multiple distinct peptide motifs were identified for p60(c-src) protein tyrosine kinase. Using the identified peptide substrates as templates, potent and highly specific pseudosubstrate-based peptide inhibitors were developed.

Original languageEnglish (US)
Pages (from-to)1577-1583
Number of pages7
JournalLife Sciences
Volume62
Issue number17-18
DOIs
StatePublished - Mar 27 1998
Externally publishedYes

Keywords

  • Combinatorial chemistry
  • Protein kinase
  • Signal transduction
  • Synthesis peptide libraries

ASJC Scopus subject areas

  • Pharmacology

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