Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...
Reexamination Certificate
2007-08-07
2007-08-07
Nashed, Nashaat T. (Department: 1656)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
C435S015000, C435S025000, C435S026000, C435S091500, C435S091500, C435S091500
Reexamination Certificate
active
10884181
ABSTRACT:
Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.
REFERENCES:
patent: 5658739 (1997-08-01), Woods, Jr.
patent: 5693515 (1997-12-01), Clark et al.
patent: 5698401 (1997-12-01), Fesik et al.
patent: 5804390 (1998-09-01), Fesik et al.
patent: 97/18469 (1997-05-01), None
patent: 97/18471 (1997-05-01), None
patent: 98/48264 (1998-10-01), None
Appelt et al., “Design of enzyme inhibitors using iterative protein crystallographic analysis,”J. Med. Chem., 34:1925-1934 (1991).
Borman, “Advance in NMR of Macromolecules,”Chem.&Eng. News, 76:55-56 (1998).
Chen et al., “Biased combinatorial libraries: novel ligands for the SH3 domain of phosphatidylinositol 3-kinase,”J. Am. Chem. Soc., 115:12591-12592 (1993).
Chen et al., “Mapping of the Binding Interfaces of the Proteins of the Bacterial Phosphotransferase System, HPr and IIAglc,”Biochemistry, 32:32-37 (1993).
Combs et al., “Protein structure-based combinatorial chemistry: discovery of non-peptide binding elements to Src SH3 domain,”J. Am. Chem. Soc., 118:287-288 (1996).
Davis et al., “Alterations in chemical shifts and exchange broadening upon peptide boronic acid inhibitor binding to α-lytic protease,”J. Biomolecular NMR, 10:21-27 (1997).
Fejzo et al., “The SHAPES strategy: an NMR-based approach for lead generation in drug discovery,”Chem.&Biol., 6(10):755-769 (1999).
Hajduk et al., “High-throughput nuclear magnetic resonance-based screening,”J. Med. Chem., 42(13):2315-2317 (1999).
Hajduk et al., “Discovery off Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR,”J. Am. Chem. Soc., 119:5818-5827 (1997).
He et al., “Design and synthesis of new leads for PKC bisubstrate inhibitors,”Bioorganic&Medicinal Chemistry Letters, 4:2845-2850 (1994).
Hrovat et al., “Backbone dynamics of oxidized and reducedD. vulgarisflavodoxin in solution,”J. Biomolecular NMR, 10:53-62 (1997).
Labrou et al., “Molecular modelling for the design of chimaeric biomimetic dye-ligands and their interaction with bovine heart mitochondrial malate dehydrogenase,”Biochem. J., 315:695-703 (1996).
Labrou et al., “Oxaloacetate Decarboxylase: On the Mode of Interaction with Substrate-Mimetic Affinity Ligands,”Arch. Biochem. Biophys., 321(1):61-70 (1995).
Labrou et al., “The Interaction ofCandida boidinniiFormate Dehydrogenase with a New Family of Chimeric Biomimetic Dye-Ligands,”Arch. Biochem. Biophys., 316(1):169-178 (1995).
Labrou et al., “Biomimetic-dye affinity chromatography for the purification of mitochondrial L-malate dehydrogenase from bovine heart,”J. Biotechnol., 45:185-194 (1996).
Lee et al., “Rapid corepressor exchange from thetrp-repressor/operator complex: an NMR study of [ul-13C/15N]-L-tryptophan,”J. Biomol. NMR, 5(4):367-375 (1995).
LeMaster, “Deuteration in protein proton magnetic resonance,”Methods Enzymol., 177:23-43 (1989).
Moore, “NMR techniques for characterization of ligand binding: Utility for lead generation and optimization in drug discovery,”Biopolymers, 51(3):221-243 (1999).
Moore, “NMR screening in drug discovery,”Curr. Opin. Biotechnol., 10(1):54-58 (1999).
Morken et al., “Exploring the leucine-proline binding pocket of the Src SH3 domain using structure-based, split-pool synthesis and affinity-based selection,”J. Am. Chem. Soc., 120:30-36 (1998).
Muchmore et al., “Expression and nitrogen-15 labeling of proteins for proton and nitrogen-15 nuclear magnetic resonance,”Methods Enzymol., 177:44-73 (1989).
Pervushin et al., “Attenuated T2relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution,”Proc. Natl. Aad. Sci. USA, 94:12366-12371 (1997).
Pervushin et al., “Transverse Relaxation-Optimized Spectroscopy (TROSY) for NMR Studies of Aromatic Spin Systems in13C-Labeled Proteins,”J. Am. Chem. Soc., 120:6394-6400 (1998).
Reilly and Fairbrother, “A novel isotope labeling protocol for bacterially expressed proteins,”J. Biomolecular NMR, 4:459-462 (1994).
Reinstein et al., “Fluorescence and NMR investigations on the ligand binding properties of adenylate kinases,”Biochem., 29:7440-7450 (1990).
Rozwarski et al., “Modification of the NADH of the isoniazid target (InhA) frommycobacterium tuberculosis,” Science, 279:98-102 (1998).
Salzmann et al., “TROSY-type Triple-Resonance Experiments for Sequential NMR Assignments of Large Proteins,”J. Am. Chem. Soc., 121:844-848 (1999).
Scheffzek et al., “Crystal structure of the complex of UMP/CMP kinase fromDictyostelium discoideumand the bisubstrate inhibitorP1-(5′-Adenosyl) P5-(5′-Uridyl) pentaphosphate (UP5A) and Mg2+at 2.2 Å: implications for water-mediated specificity,”Biochem., 35:9716-9727 (1996).
Sem and Kasper, “Geometric relationship between the nicotinamide and isoalloxazine rings in NADPH-cytochrome P-450 oxidoreductase: implications for the classification of evolutionarily and functionally related flavorproteins,”Biochem., 31:3391-3398 (1992).
Sem et al., “NMR Spectroscopic Studies of the DNA-binding Domain of the Monomer-binding Nuclear Orphan Receptor, Human Estrogen Related Receptor-2,”J. Biological Chem., 272(29):18038-18043 (1997).
Sem and Coutts, “Accelerating Drug Discovery at Triad Biotechnology,”Solutions, pp. 9 (1998).
Sem and Coutts, “Accelerating Drug Discovery at Triad Biotechnology,”Solutions, pp. 11 (1998).
Shuker et al., “Discovering High-Affinity Ligands for Proteins: SAR by NMR,”Science, 274:1531-1534 (1996).
van Nuland et al., “The NMR determination of the IIAmt1binding site on HPr of theEscherichia coliphosphoenol pyruvate-dependent phosphotransferase system,”FEBS, 315:11-15 (1993).
Venters et al., “High-level2H/13C/15N labeling of proteins for NMR studies,”J. Biomol. NMR, 5:339-344 (1995).
Wemmer and Williams, “Use of nuclear magnetic resonance in probing ligand-macromolecule interactions,”Methods Enzymol., 239:739-767 (1994).
Wüthrich, “The Second decade-into the third millenium,”Nature Structural Biology, Nature Structural Biology NMR Supplement: 492-495 (1998).
Yamazaki et al., “A suite of triple resonance NMR experiments for the backbone assignment of15N,13C,2H labeled proteins with high sensitivity,”J. Am. Chem. Soc., 116:11655-11666 (1994).
Li et al., “The inter-ligand Overhauser effect: A powerful new NMR approach for mapping structural relationships of macrolecular ligands,”J. Biomol. NMR, 15:71-76 (1999).
Medek et al., “The Use of Differential Chemical Shifts for Determining the Binding Site Location and Orientation of Protein-Bound Ligands,”J. Am. Chem. Soc., 122:1241-1242 (2000).
Pellecchia Maurizio
Sem Daniel S.
Tempczyk-Russell Anna
Nashed Nashaat T.
Triad Therapeutics, Inc.
LandOfFree
NMR-solve method for rapid identification of bi-ligand drug... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with NMR-solve method for rapid identification of bi-ligand drug..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and NMR-solve method for rapid identification of bi-ligand drug... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3893151