Peptidomimetic competitive inhibitors of protein tyrosine phosphatases.
This review discusses the development of the active site-directed protein tyrosine phosphatase (PTP) inhibitors based on peptides and some closely related nonpeptidic scaffolds. A straightforward approach is to substitute various nonhydrolyzable analogs for the phosphotyrosine (pTyr) of optimal or physiological phosphopeptide substrates of PTPs. The advances in small molecule peptidic PTP inhibitors and their nonpeptidic derivatives have been greatly aided by X-ray crystallographic and NMR spectrometric studies. Given the importance of PTPs in disease-associated signal transduction and the continuing progress in PTP drug discovery, some clinically useful PTP inhibitors may emerge in the near future.
Shen
Kui
K
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA. kshen01@uic.edu
Qi
Lixin
L
Stiff
Lynn
L
D000818:Animals; D001667:Binding, Competitive; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D019000:Phosphotyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010455:Peptides; D057786:Peptidomimetics; D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases