Protein-Tyrosine Phosphatase Inhibition by a Peptide Containing the Phosphotyrosyl Mimetic, L-O-Malonyltyrosine (L-OMT)

Kole, Hemanta K.; Akamatsu, Miki; Ye, Bin; Yan, Xinjian; Barford, David; Roller, Peter P.; Burke, Terrence R.

doi:10.1006/bbrc.1995.1573

Cited by 72 publications

(51 citation statements)

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“…For example, vanadate and its derivatives such as peroxovanadium complexes are one of the best characterized PTP inhibitors, but appear to be nonspecific among the PTP family members (Swarup et al, 1982, Posner et al, 1994, Huyer et al, 1997. PTP substrate analogues, in which the cleavable O-P linkage has been replaced by PTP-resistant chemical linkage, such as sulfotyrosine, thiophosphotyrosine, O, O-dicar boxymethyltyrosine, phosphonomethyl phenylalanine, and 4-[difluoro(phosphono)methyl]phenylalanine, have been shown as potent inhibitors of PTPs (Burke et al, 1994, Liotta et al, 1994, Kole et al, 1995, Burke et al, 1996, Huyer et al, 1998, Desmarais et al, 1999. Particularly, phosphonate compounds incorporated in peptides are being developed as relatively selective inhibitors of PTPs (Chen et al, 1995, Taing et al, 1999.…”

Section: Introductionmentioning

confidence: 99%

Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate

Heo

Ryu²,

Park³

et al. 2002

Exp Mol Med

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Abbreviations: PTP, protein tyrosine phosphatase; PTK, protein tyrosine kinase; SHP-1, SH2 domain containing protein tyrosine phosphatase-1; pNPP, p-nitrophenyl phosphate; PM, phosphomolybdate; PT, phosphotungstate; LAR, leukocyte common antigenrelated protein tyrosine phosphatase; PP1, human protein phosphatase 1; CIP, alkaline phosphatase of calf intestine; OBA, 2-(Oxalylamino)benzoic acid; bpV, Bis-peroxo(bipyridine)oxovanadate. Abstract

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Section: Introductionmentioning

confidence: 99%

Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate

Heo

Ryu²,

Park³

et al. 2002

Exp Mol Med

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“…11, 12 A number of non-hydrolyzable phosphate mimics have been developed as PTP inhibitors including aryl α-ketocarboxylic acids, 13-17 2-(oxalylamino)benzoic acids, 18 difluoromethylenesulfonates, 19, 20 squaric acids, 21 difluoromethylenephosphonates, 22 and O-malonyltyrosine. 23 However, since all PTPs share the same signature motif in the catalytic domain, it is usually necessary to extend inhibitors outside of the catalytic site to gain selectivity and improve potency. Incorporating pTyr mimics into peptide templates is one method to improve the activity of inhibitors.…”

Section: Ptp Inhibitorsmentioning

confidence: 99%

A two stage click-based library of protein tyrosine phosphatase inhibitors

Xie

Seto

2007

Bioorganic & Medicinal Chemistry

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Protein tyrosine phosphatases (PTPs) are important regulators of signal transduction pathways. Potent and selective PTP inhibitors are useful for probing these pathways and also may serve as drugs for the treatment of a variety of diseases including type 2 diabetes and infection by the bacterium Yersinia pestis. In this report Cu(I)-catalyzed 'click' cycloaddition reactions between azides and alkynes were employed to generate two sequential libraries of PTP inhibitors. In the first round library methyl 4-azidobenzoylformate was reacted with 56 mono-and diynes. After hydrolysis of the methyl esters, the resulting α-ketocarboxylic acids were assayed in crude form against the Yersinia PTP and PTP1B. Four compounds were selected for further evaluation, and one compound was chosen as the lead for generation of the second round library. This lead compound was modified by conversion of an alcohol into an azide group, and the resulting azide was reacted with the same 56 mono-and diynes that were used in the first generation library. After screening the crude inhibitors against the Yersinia PTP and PTP1B, four compounds were selected and evaluated in pure form against the Yersinia PTP, PTP1B, TCPTP, LAR and CD45. The best bis(α-ketocarboxylic acid) inhibitor 34 had an IC 50 value of 550 nM against the Yersinia PTP, and an IC 50 value of 710 nM against TCPTP. The most potent inhibitor containing a single α-ketocarboxylic acid group 32 had IC 50 values of 2.1, 5.7 and 2.6 μM against the Yersinia PTP, PTP1B and TCPTP, respectively.

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“…To address this difficulty, we prepared phosphotyrosylmimic peptides that use malonic acid rather than phosphate residues at tyrosine sites. Malonyl-tyrosine residues appear to mimic the phosphotyrosine conformation in proteins and evade the action of cellular enzymes targeted to phosphotyrosine (19,20). The malonyltyrosyl-peptides contain the sequence surrounding tyrosine-537 in ER (12,13) (see Table 1).…”

Section: Peptide Antitumor Effects In Vitro and In Vivomentioning

confidence: 99%

Peptide Antiestrogens for Human Breast Cancer Therapy

Pietras¹

2001

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Protein-Tyrosine Phosphatase Inhibition by a Peptide Containing the Phosphotyrosyl Mimetic, L-O-Malonyltyrosine (L-OMT)

Cited by 72 publications

References 0 publications

Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate

Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate

A two stage click-based library of protein tyrosine phosphatase inhibitors

Peptide Antiestrogens for Human Breast Cancer Therapy

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