A fragment-based selection approach for the discovery of peptide macrocycles targeting protein kinases

Elizabeth Restituyo, Karla Camacho-Soto, Indraneel Ghosh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Protein kinases are implicated in diverse signaling cascades and have been targeted with small molecules that typically bind the conserved ATP-binding active site. These inhibitors are often promiscuous and target multiple protein kinases, which has led to the development of alternate strategies to discover selective ligands. We have recently described a fragment-based selection approach, where a small-molecule warhead can be non-covalently tethered to a phage-displayed library of cyclic peptides. This approach led to the conversion of the promiscuous kinase inhibitor, staurosporine, into a selective bivalent inhibitor.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalMethods in Molecular Biology
Volume1248
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Allosteric inhibitors
  • Bivalent inhibitors
  • Fragment-based ligand discovery
  • Peptide macrocycles
  • Phage display
  • Protein kinases
  • Solid-phase peptide synthesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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