A new type of synthetic peptide library for identifying ligand-binding activity

Kit S. Lam, Sydney E. Salmon, Evan M. Hersh, Victor J. Hruby, Wieslaw M. Kazmierskit, Richard J. Knappt

Research output: Contribution to journalArticlepeer-review

1625 Scopus citations

Abstract

Our aim was to improve techniques for drug development by facilitating the identification of small molecules that bind with high affinity to acceptor molecules (for example, cell-surface receptors, enzymes, antibodies) and so to mimic or block their interaction with the natural ligand1,2. Previously such small molecules have been characterized individually on a serial basis. The systematic synthesis and screening of peptide libraries of defined structure represents a new approach. For relatively small libraries, predetermined sequence variations on solid-phase supports have been used3,4, and large libraries have been produced using a bacteriophage vector into which random oligodeoxynucleotide sequences have been introduced5-8, but these techniques have severe limitations. Here we investigate an alternative approach to synthesis and screening of peptide libraries. Our simple methodology greatly enhances the production and rapid evaluation of random libraries of millions of peptides so that acceptor-binding ligands of high affinity can be rapidly identified and sequenced, on the basis of a 'one-bead, one-peptide' approach.

Original languageEnglish (US)
Pages (from-to)82-84
Number of pages3
JournalNature
Volume354
Issue number6348
DOIs
StatePublished - Nov 7 1991

ASJC Scopus subject areas

  • General

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