ArticleBioorganic & medicinal chemistry2008
Allele-specific inhibition of divergent protein tyrosine phosphatases with a single small molecule.
Article in Bioorganic & medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Site-Specific and Fluorescently Enhanced Installation of Post-Translational Protein Modifications via Bifunctional Biarsenical Linker.ACS omega · 2024Article
- The Allosteric Site on SHP2's Protein Tyrosine Phosphatase Domain is Targetable with Druglike Small Molecules.ACS omega · 2018Article
- Optimized allosteric inhibition of engineered protein tyrosine phosphatases with an expanded palette of biarsenical small molecules.Bioorganic & medicinal chemistry · 2018Article
- A missense methionine mutation augments catalytic activity but reduces thermal stability in two protein tyrosine phosphatases.Biochemical and biophysical research communications · 2016Article
- Rational design of allosteric-inhibition sites in classical protein tyrosine phosphatases.Bioorganic & medicinal chemistry · 2015Article
- Probing the target-specific inhibition of sensitized protein tyrosine phosphatases with biarsenical probes.Organic & biomolecular chemistry · 2015Article
- Targeting a cryptic allosteric site for selective inhibition of the oncogenic protein tyrosine phosphatase Shp2.Biochemistry · 2015Article
- Investigating mammalian tyrosine phosphatase inhibitors as potential 'piggyback' leads to target Trypanosoma brucei transmission.Chemical biology & drug design · 2013Article
- Specific inhibition of sensitized protein tyrosine phosphatase 1B (PTP1B) with a biarsenical probe.Bioconjugate chemistry · 2012Article
- Target-specific control of lymphoid-specific protein tyrosine phosphatase (Lyp) activity.Bioorganic & medicinal chemistry · 2010Article
- Chemical rescue of protein tyrosine phosphatase activity.Chemical communications (Cambridge, England) · 2010Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
A central challenge of chemical biology is the development of small-molecule tools for controlling protein activity in a target-specific manner. Such tools are particularly useful if they can be systematically applied to the members of large protein families. Here we report that protein tyrosine phosphatases can be systematically 'sensitized' to target-specific inhibition by a cell-permeable small molecule, Fluorescein Arsenical Hairpin Binder (FlAsH), which does not inhibit any wild-type PTP investigated to date. We show that insertion of a FlAsH-binding peptide at a conserved position in the PTP catalytic-domain's WPD loop confers novel FlAsH sensitivity upon divergent PTPs. The position of the sensitizing insertion is readily identifiable from primary-sequence alignments, and we have generated FlAsH-sensitive mutants for seven different classical PTPs from six distinct subfamilies of receptor and non-receptor PTPs, including one phosphatase (PTP-PEST) whose three-dimensional catalytic-domain structure is not known. In all cases, FlAsH-mediated PTP inhibition was target specific and potent, with inhibition constants for the seven sensitized PTPs ranging from 17 to 370 nM. Our results suggest that a substantial fraction of the PTP superfamily will be likewise sensitizable to allele-specific inhibition; FlAsH-based PTP targeting thus potentially provides a rapid, general means for selectively targeting PTP activity in cell-culture- or model-organism-based signaling studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.