Abstract
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 language | English (US) |
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Pages (from-to) | 677-682 |
Number of pages | 6 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 4 |
Issue number | 5 |
DOIs | |
State | Published - May 1996 |
Externally published | Yes |
Keywords
- Combinatorial libraries
- p60
- Peptide substrate
- Protein tyrosine kinase
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science