Potent pseudosubstrate-based peptide inhibitors for p60(c-src) protein tyrosine kinase

Qiang Lou, Margaret E. Leftwich, R. Trent McKay, Sydney E. Salmon, Lenka Rychetsky, Kit Lam

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We recently reported the identification of GIYWHHY as an efficient and specific substrate for p60(c-src) protein tyrosine kinase (PTK) by screening a secondary random peptide library (Q. Lou et al., Bioorg. Med. Chem., 4: 677-682, 1996). Based on the primary structure of GIYWHHY, we designed and synthesized several pseudosubstrate-based peptide inhibitors. Some of these peptide inhibitors are highly potent and specific with IC50 in the low micromolar range. Because both YIYGSFK and GIY-WHHY are efficient and specific substrates for p60(c-src) PTK, chimeric branched peptides based on these two sequences were synthesized. These branched peptides inhibit p60(c- src) PTK with high potency, indicating that the enzyme-active site of p60(c- src) PTK can accommodate more than a linear motif. This may explain why seemingly several peptides with very different linear structures can all be phosphorylated by this enzyme.

Original languageEnglish (US)
Pages (from-to)1877-1881
Number of pages5
JournalCancer Research
Volume57
Issue number10
StatePublished - May 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Lou, Q., Leftwich, M. E., McKay, R. T., Salmon, S. E., Rychetsky, L., & Lam, K. (1997). Potent pseudosubstrate-based peptide inhibitors for p60(c-src) protein tyrosine kinase. Cancer Research, 57(10), 1877-1881.