TY - JOUR
T1 - Potent pseudosubstrate-based peptide inhibitors for p60(c-src) protein tyrosine kinase
AU - Lou, Qiang
AU - Leftwich, Margaret E.
AU - McKay, R. Trent
AU - Salmon, Sydney E.
AU - Rychetsky, Lenka
AU - Lam, Kit
PY - 1997/5/15
Y1 - 1997/5/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9157979
AN - SCOPUS:0030963144
VL - 57
SP - 1877
EP - 1881
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 10
ER -