Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1995-03-31
1997-11-18
Tsang, Cecilia J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
560 76, 562 65, 514561, 514563, 514570, 514 2, C07C 57145, A61K 3119, A61K 31195, A61K 3800
Patent
active
056889925
ABSTRACT:
The present invention relates to non-phosphorus containing O-malonyltryrosyl compounds, derivatives thereof, uses of the O-malonyltryrosyl compounds in the synthesis of peptides, and O-malonyltryrosyl compound-containing peptides. The O-malonyltyrosyl malonyltyrosyl compounds and O-malonyltryrosyl compound-containing peptides of the present invention are uniquely stable to phosphotases, capable of crossing cell membranes, suitable for application to peptide synthesis of O-malonyltryrosyl compound-containing peptides, and amenable to prodrag defivatization for delivery into cells. The present invention also provides for O-malonyltryrosyl compound-containing peptides which exhibit inhibitory potency against binding interactions of receptor domains with phosphotyrosyl-containing peptide ligands.
REFERENCES:
patent: 5200546 (1993-04-01), Burke, Jr. et al.
Hunter, T. Protein-Tyrosine Phosphatases: Theother side of the coin. Cell, 58:1013-1016, Sep. 1989.
Burke, Jr., T.R., et al. (1991) Preparation of Hydrolytically Stable Analog of O-Phosphotyrosine Potentially Suitable for Peptide Synthesis, Synthesis 11:1019-1020.
Burke, Jr., T.R., et al. (1993) Synthesis of 4-Phosphono(Difluoromethly)-D-L-Phenylalanine and N-Boc and N-Fmoc Derivatives Suitable Protected for Solid-Phase Synthesis of Nonhydrolyzable Phosphotyrosyl Peptide Analogues, Tetrahedron Letters 34:4125-4128.
Burke, Jr., T.R., et al. (1993) Preparation of Fluoro- and Hydroxy-4-Phosphonomethyl-D,L-Phenylalanine Suitably Protected for Solid-Phase Synthesis of Peptides containing Hydrolytically Stable Analogues of O-Phosphotyrosine, J. Organ Chem. 58:1336-1340.
Burke, Jr., T.R., et al. (1994) Nonhydrolyzable Phosphotryosyl Mimetics for the Preparation of Phosphotase-Resistant SH2 Domain Inhibitos, Biochemistry 33:6490-6494.
Burke, Jr., T.R., et al. (1994) Cyclic Peptide Inhibitors of Phosphatidylinositol 3-Kinase p85 SH2 Domain Binding, Biochem. Biophys. Res. Commun. 201:1148-1153.
Burke, Jr., T.R., et al. (1994) Potent Inhibition of Insulin Receptor Dephosphorylation by a Hexamer Peptide Containing the Phosphotyrosyl Mimetic F2Pmp, Biochem. Biophys. Res. Commun. 204:129-134.
Burke, Jr., T.R., et al. (1995) Non Phosphorus Containing Phosphotyrosyl Mimetics Amenable to Prodrug Derivatization and Their use in Solid-Phase Peptide Synthesis of SH2 Domain and phosphatase Inhibitors, 209th National American Chemical Society Meeting, Annaheim, CA, MEDI 14.
Burke, Jr., T.R., et al. (1995) Conformationally Constrained Phosphotyrosyl Mimetics Designed as Monomeric SH2 Domain Inhibitors, J. Med. Chem. (Exhibit I).
Corey, S.D., et al. (1993) EPSP Synthase Inhibitor Design III. Synthesis & Evaluation of a New 5-Oxamic Acid Analog of ESPS which Incorporates a Malonate Ether as a 3-Phosphate Mimic, Bioorg. Med. Lett. 3:2857-2862.
Domchek, S.M., et al. (1992) Inhibition of SH2 Domain/Phosphoprotein Association by a Nondrolyzable Phosphonopeptide, Biochemistry 31:9865-9870.
Kole, H., et al. (1995?) Protein-Tyrosine Phosphatase Inhibition by a Peptide Containing the Phosphotyrosyl Mimetic, L-O-Malonyltyrosine (L-OMT), Biochem. Biophys. Res. Commun.
Marzabadi, M.R., et al. (1992) Design & Synthesis of a Novel EPSP Synthase Inhibitor Based on its Ternary Complex with Shikimate-3-Phosphate and Glyphosate, Bioorg. Med. Chem. Lett. 2:1435-1440.
Miller, M.J., et al. (1993) EPSP Synthase Inhibitor Design II. The Importance of the 3-Phosphate Group for Ligand Binding at the Shikimate-3-Phosphate Site & the Identification of 3-Malonate Ethers as Novel 3-Phosphate Mimetics, Bioorg. Med. Chem. Lett. 7:1435-1440.
Nomizu, M., et al. (1994) Synthesis of Phosphonomethyl-Phenylalanine and Phosphotyrosine Containing Cyclics Peptides as Inhibitors of Protein Tyrosine Kinase/SH2 Interactions, Tetrahedron 50:2691-2702.
Nomizu, M., et al. (1994) Synthesis and Structure of SH2 Binding Peptides Containing 4-Phosphonomethyl-Phenylalanine and Analogs, Peptide Chemistry: Proceedings of the 31st Japanese Symposium. Kobe: Protein Research Foundation, Osaka, Japan.
Otaka, A., et al. (1993) Synthesis and Structure Activity Studies of SH2 Binding Peptides Containing Hydrolytically Stable Analogs of O-Phosphotyrosine, Peptides: Chemistry and Biology: Proceedings of the Thirteenth American Peptide Symposium. Edmonton, Alberta, Canada: ESCOM Publishers, Leiden, The Netherlands.
Shoelson, S.E., et al. (1991) Solid Phase Synthesis of Nonhydrolyzable Phosphotyrosyl Peptide Analogs with N(alpha)-Fmoc-(O,O-di-tert-butyl)phosphono-para-methylphenylalanine, Tetrahedron Letters 32;6061-6064.
Sikorski, J.H., et al. (1993) EPSP Synthase: the Design and Synthesis of Bisubstrate Inhibitors Incorporating Novel 3-Phosphate Mimics, Phosphorus, Sulfur, and Silicon 76:115-118.
Sikorski, J.H., et al. (1990) An Enzyme-Targeted Herbicide Design program Based on EPSP Synthase: Chemical Mechanism and Glyphosate Inhibition Annu. Symp.!.
Smyth, M.S., et al. (1992) A general Method for the Preparation of Benzylic Alpha, Alpha-Difluorophosphonic Acids; Non-Hydrolyzable Mimetics of Phosphotyrines, Tetrahedron Lett. 33:4137-4140.
Sternbach, David D., Progress Toward Small Molecule Inhibitors of src SH3-SH2 Phosphoprotein Interactions. 209th American Chemical Society Meeting, Anaheim, California, Apr. 2-6, 1995. MEDI 144.
Tan, Y.H., (1993) Yin and Yang of Phosphorylation in Cytokine Signaling, Science 262:376-377.
Akamatsu Miki
Burke, Jr. Terrence R.
Kole Hemanta K.
Roller Peter R.
Yan Xinjian
The United States of America as represented by the Department of
Tsang Cecilia J.
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