Inhibition of protein tyrosine phosphatases PTP1B and CD45 by sulfotyrosyl peptides.
Sulfotyrosyl peptides corresponding to the known high-affinity substrate phosphotyrosyl peptide sequences in casein and the autophosphorylation sites of insulin receptor and EGF receptor were investigated as inhibitors of protein tyrosine phosphatases PTP1B and CD45. These peptides inhibit both PTP1B and CD45 in the micromolar range competitively and reversibly. The elements required for inhibition were investigated by truncation and substitution of these peptides. Acidic residues N-terminal to the sulfotyrosyl residues are essential for high-affinity binding to PTP1B. The recognition elements required for inhibition of PTP1B and CD45 are different and this suggests the possibility of identifying selective active-site-directed inhibitors for these enzymes.
Desmarais
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Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research, Dorval, Pointe-Claire, H9R 4P8, Canada.
Jia
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Ramachandran
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D001665:Binding Sites; D002364:Caseins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017493:Leukocyte Common Antigens / Q000187:drug effects*; D008958:Models, Molecular; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity; D013457:Sulfur Compounds / Q000494:pharmacology*
D002364:Caseins; D004791:Enzyme Inhibitors; D010455:Peptides; D013457:Sulfur Compounds; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases