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Special Issue "Protein-Tyrosine Phosphatase Inhibitors"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: 30 January 2018

Special Issue Editors

Guest Editor
Prof. Jeroen den Hertog

1. Hubrecht Institute–Koninklijke Nederlandse Akademie van Wetenschappen (KNAW) and University Medical Center Utrecht, Utrecht, The Netherlands
2. Institute of Biology Leiden, Leiden University, Leiden, The Netherlands
Website | E-Mail
Interests: protein-tyrosine phosphatase; signaling; PTEN; SHP2; RPTPalpha; zebrafish; gastrulation; cancer; Noonan Syndrome
Guest Editor
Prof. Rob M. J. Liskamp

School of Chemistry, University of Glasgow, Joseph Black Building, University Avenue, Glasgow, UK and Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Website1 | Website2 | E-Mail
Interests: peptidomimetics; protein mimics; synthetic vaccines; synthetic antibodies; protease inhibitors; protein phosphatase inhibitors; electrophilic traps; cancer; infections; inflammation

Special Issue Information

Dear Colleagues,

Protein-tyrosine phosphatases counteract protein-tyrosine kinases and, hence, have a central role in development and disease, as regulators of phosphotyrosine levels in cellular proteins. Protein-tyrosine phosphatases have been heralded as drug targets for decades, particularly for conditions such as cancer and diabetes. Over the years, many catalytic site-directed protein-tyrosine phosphatase inhibitors have been generated; however, the catalytic sites of protein-tyrosine phosphatases are highly conserved, which compromises the selectivity of small molecule compounds. In addition, the substrates of protein-tyrosine phosphatases contain negatively-charged phosphotyrosine, which hampers the transduction of substrate-mimetic inhibitors across the cell membrane. Recently, several allosteric inhibitors have been developed that are highly selective and do not contain negative charges. Looking forward, there is a bright future for small molecule inhibitors of protein-tyrosine phosphatases.

Prof.  Jeroen den Hertog
Prof. Rob M. J. Liskamp
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • protein-tyrosine phosphatases
  • (covalent) inhibitors
  • small molecules
  • peptidomimetics
  • allosteric inhibitors
  • cancer
  • diabetes

Published Papers (2 papers)

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Research

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Open AccessArticle Novel Mixed-Type Inhibitors of Protein Tyrosine Phosphatase 1B. Kinetic and Computational Studies
Molecules 2017, 22(12), 2262; doi:10.3390/molecules22122262
Received: 21 November 2017 / Revised: 13 December 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
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Abstract
The Atlas of Diabetes reports 415 million diabetics in the world, a number that has surpassed in half the expected time the twenty year projection. Type 2 diabetes is the most frequent form of the disease; it is characterized by a defect in
[...] Read more.
The Atlas of Diabetes reports 415 million diabetics in the world, a number that has surpassed in half the expected time the twenty year projection. Type 2 diabetes is the most frequent form of the disease; it is characterized by a defect in the secretion of insulin and a resistance in its target organs. In the search for new antidiabetic drugs, one of the principal strategies consists in promoting the action of insulin. In this sense, attention has been centered in the protein tyrosine phosphatase 1B (PTP1B), a protein whose overexpression or increase of its activity has been related in many studies with insulin resistance. In the present work, a chemical library of 250 compounds was evaluated to determine their inhibition capability on the protein PTP1B. Ten molecules inhibited over the 50% of the activity of the PTP1B, the three most potent molecules were selected for its characterization, reporting Ki values of 5.2, 4.2 and 41.3 µM, for compounds 1, 2, and 3, respectively. Docking and molecular dynamics studies revealed that the three inhibitors made interactions with residues at the secondary binding site to phosphate, exclusive for PTP1B. The data reported here support these compounds as hits for the design more potent and selective inhibitors against PTP1B in the search of new antidiabetic treatment. Full article
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
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Review

Jump to: Research

Open AccessReview Vanadium Compounds as PTP Inhibitors
Molecules 2017, 22(12), 2269; doi:10.3390/molecules22122269
Received: 30 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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Abstract
Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought
[...] Read more.
Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential. Full article
(This article belongs to the Special Issue Protein-Tyrosine Phosphatase Inhibitors)
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