Dentification of GIYWHHY as a novel peptide substrate for human p60c-src protein tyrosine kinase

Qiang Lou, Margaret E. Leftwich, Kit Lam

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


We have recently determined that -Ile-Tyr-were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase (Lou, Q. et al., Lett. Peptide Sci., 1995, 2, 289). Here, we report on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine). This secondary library was screened for its ability to be phosphorylated by p60c-src PTK using [γ32P]ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate.

Original languageEnglish (US)
Pages (from-to)677-682
Number of pages6
JournalBioorganic and Medicinal Chemistry
Issue number5
StatePublished - May 1996
Externally publishedYes


  • Combinatorial libraries
  • p60
  • Peptide substrate
  • Protein tyrosine kinase

ASJC Scopus subject areas

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


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