Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1996-10-31
1999-11-23
Green, Lora M.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
436501, 436173, G01N 3353, G01N 2408
Patent
active
059898275
ABSTRACT:
The present invention provides a process of designing compounds which bind to a specific target molecule. The process includes the steps of a) identifying a first ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; b) identifying a second ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; c) forming a ternary complex by binding the first and second ligands to the target molecule; d) determining the three dimensional structure of the ternary complex and thus the spatial orientation of the first and second ligands on the target molecule; and e) linking the first and second ligands to form the drug, wherein the spatial orientation of step (d) is maintained.
REFERENCES:
patent: 5270163 (1993-12-01), Gold et al.
patent: 5306619 (1994-04-01), Edwards et al.
patent: 5698401 (1997-12-01), Fesik et al.
A. Bax et al., "Methodological Advances in Protein NMR", Accounts of Chemical Research, vol. 26, No. 4, (1993), pp. 131-138.
A. Bax et al., "An Efficient 3D NMR Technique for Correlating the Proton and .sup.15 N Backbone Amide Resonances With the .alpha.-Carbon of the Preceding Residue in Uniformly .sup.15 N/.sup.13 C Enriched Proteins", Journal Of Biomolecular NMR, vol. 1, (1991), pp. 99-104.
A. Bax et al., "Optimized Recording of Heteronuclear Multidimensional NMR Spectra Using Pulsed Field Gradients", Journal of Magnetic Resonance, vol. 99, (1992), pp. 638-643.
G. Bodenhausen et al., "Natural Abundance Nitrogen-15 NMR by Enhanced Heteronuclear Spectroscopy", Chemical Physics Letters, vol. 69, No. 1, (1980), pp. 185-189.
S.D. Clark et al., "Coregulation of Collagenase and Collagenase Inhibitor Production by Phorbol Myristate Acetate in Human Skin Fibroblasts", Archives of Biochemistry and Biophysics, vol. 241, No. 1, (1985), pp. 36-44.
D.A. Egan et al., "Equilibrium Denaturation of Recombinant Human FK Binding Protein in Urea", Biochemistry, vol. 32, No. 8, (1993), pp. 1920-1927.
S.D. Emerson et al., "Solution Structure of the Ras-Binding Domain of c-Raf-1 and Identification of Its Ras Interaction Surface", Biochemistry, vol. 34, No. 21, (1995), pp. 6911-6918.
S.W. Fesik et al., "Heteronuclear Three-Dimensional NMR Spectroscopy. A Strategy for the Simplification of Homonuclear Two-Dimensional NMR Spectra", Journal of Magnetic Resonance, vol. 78, No. 3, (1988), pp. 588-593.
G. Gemmecker et al., "An Improved Method for Selecvtively Observing Protons Attached to .sup.12 C in the Presence of .sup.1 H-.sup.13 C Spin Pairs", Journal of Magnetic Resonance, vol. 96, (1992), pp. 199-204.
S. Grzesiek et al., "Correlating Backbone Amide and Side Chain Resonances in Larger Proteins by Multiple Relayed Triple Resonance NMR", Journal of the American Chemicla Society, vol. 114, (1992), pp. 6291-6293.
L.E. Kay et al., "Three-Dimensional Triple-Resonance NMR Spectroscopy of Isotopically Enriched Proteins", Journal Of Magnetic Resonance, vol. 89, (1990), pp. 496-514.
L.E. Kay et al., "A Gradient-Enhanced HCCH-TOCSY Experiment for Recording Side-Chain .sup.1 H and .sup.13 C Correlations in H.sub.2 O Samples of Proteins", Journal of Magnetic Resonance, vol. 101, No. 6, (1993), pp. 333-337.
T.M. Logan et al., "Structural Characterization of the FK 506 Binding Protein Unfolded in Urea and Guanidine Hydrochloride", Journal of Molecular Biology, vol. 236, (1994), 637-648.
A.I. Marcy et al., "Human Fibroblast Stromelysin Catalytic Domain: Expression, Purification, and Characterization of a C-Terminally Truncated Form", Biochemistry, vol. 30, (1991), pp. 6476-6483.
D. Marion et al., "Three-Dimensional Heteronuclear NMR of .sup.15 N-Labeled Proteins", Journal of the American Society, vol. 111, (1989), pp. 1515-1517.
E.D. Matayoshi et al., "Novel Fluorogenic Substrates for Assaying Retroviral Proteases by Resonance Energy Transfer", Science, vol. 247, (1990), pp. 954-958.
D. Neri et al., "Stereospecific Nuclear Magnetic Resonance Assignments of the Methyl Groups of Valine and Leucine in the DNA-Binding Domain of the 434 Repressor by Biosynthetically Directed Fractional .sup.13 C Labelling", Biochemistry, vol. 28, (1989), pp. 7510-7516.
M. Nigles et al., "Determination of Three-Dimensional Structures of Proteins From Interproton Distance Data by Hybrid Distance Geometry-Dynamical Simulated Annealing Calculations", FEBS Letters, vol. 229, No. 2, (1989), pp. 317-324.
E.T. Olejniczak et al., "Extrapolation of Time-Domain Data With Linear Prediction Increases Resolution and Sensitivity", Journal of Magnetic Resonance, vol. 87, (1990), pp. 628-632.
Ye et al., "Purification and Characterization of the Human Stromelysin Catalytic Domain Expressed in Escherichia coli", Biochemistry, vol. 31, (1992), pp. 11231-11235.
S.P. Rucker et al., "Broadband Homonuclear Cross Polarization in 2D N.M.R. Using DIPSI-2", Molecular Physics, vol. 68, No. 2, (1989), 509-517.
G.W. Vuister et al., "Quantitative J Correlation : A New Approach for Measuring Homonuclear Three-Bond J(H.sup.N N.sup..alpha.) Coupling Constants in .sup.15 N-Enriched Proteins", Journal of American Chemical Society, vol. 115, (1993), pp. 7772-7777.
H. Weingarten et al., "Spectrophotometric Assay for Vertebrate Collagenase", Analytical Biochemistry, vol. 147, No. 2, (1985), pp. 437-440.
S. Brown et al., 15N NMR Study of [15N]Actimomycin D Complexed with d(pGpC) and DNA, J. Am. Chem. Soc. (1982), 104, 5504-5506.
J. Cheng et al., "15N NMR Relaxation Studies of the FK506 Binding Protein: Backbone Dynamics of the Uncomplexed Receptor" Biochemistry 1993, 32, 9000-9010.
D. Gorenstein et al., "31P and Two-Dimensional 31P/1H Correlated NMR Spectra of Duplex d(Ap[170]Gp[18O]Cp[16O]T) and Assignment of 31P Signals in d(ApGpCpT)2-Actinomycin D Complex" Biochemistry 1984, 23,6717-6723.
C. Lin et al., "Determination of the Major Tautomeric Form of the Covalently Modified Adenine in the (+)-CC-1065-DNA Adduct by 1H and 15N NMR Studies" Biochemistry 1990, 29, 9503-9507.
E. Nikonowicz et al., "An Efficient Procedure for Assignment of Proton, Carbon and Nitrogen Resonances in 13C/15N Labeled Nucleic Acids" J. Mol. Biol. (1993) 232, 1141-1156.
S.W. Fesik et al., "NMR Methods For Determining The Structures Of Enzyme/Inhibitor Complexes As An Aid In Drug Design", Biochemical Pharmacology, vol. 40, No. 1, 161-167 (1990).
R.P. Meadows et al., "Three-Dimensional Structure Of The FK506 Binding Protein/Ascomycin Complex In Solution By Heteronuclear Three-And Four-Dimensional NMR", Biochemistry, vol. 32, 754-765 (1993).
NMR Method Offers Shortcut To Drug Design; Science 274;1531 (1996).
Bennion, et al; Design and Synthesis of Some Substrate Analogue Inhibitors of Phospholipase A2 and Investigations by NMR and Molecular Modeling into the Binding Interactions in the Enzyme-Inhibitor Complex; J. Med. Chem 1992, 35, 2939-2951.
Fesik, eta l., NMR Methods for Determining the Structure of Enzyme/Inhibitor Complexes as an Aid in Drug Design; Biochem Pharm vol. 40, No. 1 pp. 161-167 1990.
Fesik, et al., NMR Studies of Molecular Complexes as a Tool in Drug Design; Journ of Med Chem vol. 34. No. 10 Oct. 91 p. 2937.
Roberts et al.; Crystallization and Preliminary Xray Analysis of Elctron Transfer Flavoproteins from Human and Paracoccus Denitrificans; Protein Science(1995) 4:1654-1657.
Mujeeb, et al., A Potential Gene Target in HIV-1; Rationale, Selection of a Conserved Sequence, and Determination of NMR Distance and Torsion Angle Constraints, Biochemistry 1992, 31, 9325-9338.
Fesik, NMR Structure Based Drug Design, Journ of Bio NMR 3 (1993)261-269.
Sanner et al., Geom: A New Tool for Molecular Modelling Based on Distance Geometry Calculation with NMR Data, Journ of Computer-aided Molecular Design, 3 (1989) 195-210.
Journ of China Pharmaceutical University 1992: 23(5):316.
Craik et al., Determining the Conformation of a Ligand Bound to an Enzyme; Journ of Chem Ed. vol. 68 No. 3 Mar. 1991.
Zuiderweg, et al., Modern NMR Spectroscopy of Proteins and Peptides in Solution and its Relevance to Drug Design; Perspectives in Drug Disc and Design, 1 (1993) 391-417.
Trotta, et al., 1H NMR Study of D(GCGATCGC);2 and its
Fesik Stephen W.
Hajduk Philip J.
Olejniczak Edward T.
Abbott Laboratories
Green Lora M.
Pope Lawrence S.
LandOfFree
Use of nuclear magnetic resonance to design ligands to target bi does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of nuclear magnetic resonance to design ligands to target bi, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of nuclear magnetic resonance to design ligands to target bi will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1220192