Design, synthesis, and characterization of an ATP-peptide conjugate inhibitor of protein kinase A

Aliya C. Hines, Philip A. Cole

Research output: Contribution to journalArticlepeer-review

Abstract

An ATP-peptide conjugate was synthesized as a bisubstrate analogue inhibitor of the serine/threonine kinase protein kinase A. The compound was found to be a linear, competitive inhibitor with respect to ATP substrate, exhibiting a Ki of 3.8μM. The compound was noncompetitive with respect to peptide substrate. The inhibitor was shown to be selective for protein kinase A versus the closely related protein kinase C as well as tyrosine kinase Csk. This analysis provides new evidence for the dissociative transition state of protein serine/threonine kinases and illustrates a simple method to convert a low affinity peptide substrate to a selective and moderately potent inhibitor for these enzymes.

Original languageEnglish (US)
Pages (from-to)2951-2954
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number11
DOIs
StatePublished - Jun 7 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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