Development of a selective pseudosubstrate-based peptide inhibitor of pp60c-scr protein tyrosine kinase

Jinzi J. Wu, Hoang Phan, Sydney E. Salmon, Kit Lam

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Using a combinatorial peptide library method, we identified YIYGSFK as an efficient and specific peptide substrate for pp60c-scr protein tyrosine kinase (PTK) [Lam et al., Int. J. Pept. Protein Res., 45 (1995) 587]. Employing YIYGSFK as a template, we synthesized and evaluated a series of pseudosubstrate-based inhibitors for pp60c-scr. We found that the efficiency of a given inhibitor was highly dependent on the specific tyrosine analog used at the phosphorylation site of the substrate. One of these pseudosubstrate inhibitors, YI(2′-Nal)GSFK, selectively inhibited the kinase activity of pp60c-scr, with a Ki of 24 μM. This peptide inhibitor exhibited selectivity for pp60c-scr as compared to other PTKs tested, such as c-Abl and Bcr-Abl. Our results suggest that selective inhibitors for a specific PTK can be developed when the structure of a specific and efficient small peptide substrate for this PTK can be used as a template for structure modification.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalInternational Journal of Peptide Research and Therapeutics
Volume3
Issue number5
StatePublished - 1996
Externally publishedYes

Keywords

  • Kinetics
  • Peptide substrate
  • Pseudosubstrate inhibitor
  • Selectivity

ASJC Scopus subject areas

  • Biochemistry
  • Bioengineering
  • Molecular Medicine
  • Drug Discovery
  • Analytical Chemistry

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