Natural products with protein tyrosine phosphatase inhibitory activity.
Protein tyrosine phosphatases (PTPs) play an essential role in maintaining the proper tyrosine phosphorylation state of proteins. Abnormal tyrosine phosphorylation has been implicated in diseases as diverse as type 2 diabetes, cancer, immune disorders and neurological disorders, and thus inhibitors of PTPs have been investigated as potential treatments of these diseases. Natural products are widely regarded to be privileged structures in drug discovery efforts, and are therefore a good starting point for the development of PTP inhibitors. Here we describe reported natural product PTP inhibitors as well as methods to screen for natural product PTP inhibitors using bioassay-guided fractionation. These methods are illustrated using the example of a family of bromotyrosine-derived PTP inhibitors isolated from two marine sponges. We also identify potential pitfalls and false-positives, in particular compounds that are oxidizing agents that react irreversibly with the PTP.
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Gavin
G
Carr
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Fabrice
F
Berrue
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Saranyoo
S
Klaiklay
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Isabelle
I
Pelletier
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada.
Melissa
M
Landry
Department of Chemistry, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE C1A 4P3, Canada. Electronic address: rkerr@upei.ca.
Russell G
RG
Kerr
D000818:Animals; D001681:Biological Assay; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D005591:Chemical Fractionation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005189:False Positive Reactions; D011161:Porifera / Q000737:chemistry*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*
D001688:Biological Products; D004791:Enzyme Inhibitors; D017027:Protein Tyrosine Phosphatases
CD45; CDC25; LAR; MPTP; Natural products; PTP1B; Protein tyrosine phosphatase; SHP-1; SHP-2; VHR