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 language | English (US) |
---|---|
Pages (from-to) | 309-316 |
Number of pages | 8 |
Journal | International Journal of Peptide Research and Therapeutics |
Volume | 3 |
Issue number | 5 |
State | Published - 1996 |
Externally published | Yes |
Keywords
- Kinetics
- Peptide substrate
- Pseudosubstrate inhibitor
- Selectivity
ASJC Scopus subject areas
- Biochemistry
- Bioengineering
- Molecular Medicine
- Drug Discovery
- Analytical Chemistry