Title:
METHOD FOR FINDING LIGANDS THAT BIND TO A DRUG TARGET USING <1>H,<1>H NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
Document Type and Number:
WIPO Patent Application WO2003054532
Kind Code:
A3
Abstract:
The invention relates to a method for finding ligands that bind to a predetermined drug target. The inventive method is based on the measuring method of nuclear magnetic resonance spectroscopy (NMR) and comprises the following steps: (A) recording the image of a two-dimensional or higher dimensional NMR correlation spectrum of the free, dissolved drug target in which at least two proton dimensions are intercorrelated as a reference spectrum; (B) recording a second, similar NMR correlation spectrum of a solution that contains the drug target and one or more test substances as the test spectrum; and (C) identifying the ligands that bind to the drug target on the basis of modifications of the NMR signals of the drug target between the test spectrum and the reference spectrum. The inventive method is especially advantageous over corresponding methods known from the art in that no labeling of the drug target with isotopes such as <13>C or <15>N is required.
Inventors:
DIERCKS TAMMO (DE)
Application Number:
PCT/DE2002/004444
Publication Date:
September 18, 2003
Filing Date:
December 04, 2002
Export Citation:
Assignee:
DIERCKS TAMMO (DE)
International Classes:
G01R33/465; G01N24/08; G01R33/46; (IPC1-7): G01R33/465; G01N33/50
Foreign References:
| US20010004528A1 | 2001-06-21 | |||
| US5698401A | 1997-12-16 |
Other References:
DIERCKS TAMMO ET AL: "Applications of NMR in drug discovery.", CURRENT OPINION IN CHEMICAL BIOLOGY, vol. 5, no. 3, June 2001 (2001-06-01), pages 285 - 291, XP002237426, ISSN: 1367-5931
BYEON IN-JA L ET AL: "Ligand Binding to the Tissue-type Plasminogen Activator Kringle 2 Domain: Structural Characterization by 1H-NMR.", BIOCHEMISTRY, vol. 34, no. 9, 1995, pages 2739 - 2750, XP002237427, ISSN: 0006-2960
CARLOMAGNO T ET AL: "COIN TACSY, a Novel Approach to Tailored Correlation Spectroscopy", JOURNAL OF MAGNETIC RESONANCE, ACADEMIC PRESS, ORLANDO, FL, US, vol. 149, no. 1, March 2001 (2001-03-01), pages 52 - 57, XP004406655, ISSN: 1090-7807
SHUKER S B ET AL: "Discovering High-Affinity Ligands for Proteins: SAR by NMR", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, no. 274, 1996, pages 1531 - 1534, XP002074440, ISSN: 0036-8075
PATERSON Y ET AL: "AN ANTIBODY BINDING SITE ON CYTOCHROME C DEFINED BY HYDROGEN EXCHANGE AND TWO-DIMENSIONAL NMR", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, vol. 249, 17 August 1990 (1990-08-17), pages 755 - 759, XP000938506, ISSN: 0036-8075
BYEON IN-JA L ET AL: "Ligand Binding to the Tissue-type Plasminogen Activator Kringle 2 Domain: Structural Characterization by 1H-NMR.", BIOCHEMISTRY, vol. 34, no. 9, 1995, pages 2739 - 2750, XP002237427, ISSN: 0006-2960
CARLOMAGNO T ET AL: "COIN TACSY, a Novel Approach to Tailored Correlation Spectroscopy", JOURNAL OF MAGNETIC RESONANCE, ACADEMIC PRESS, ORLANDO, FL, US, vol. 149, no. 1, March 2001 (2001-03-01), pages 52 - 57, XP004406655, ISSN: 1090-7807
SHUKER S B ET AL: "Discovering High-Affinity Ligands for Proteins: SAR by NMR", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, no. 274, 1996, pages 1531 - 1534, XP002074440, ISSN: 0036-8075
PATERSON Y ET AL: "AN ANTIBODY BINDING SITE ON CYTOCHROME C DEFINED BY HYDROGEN EXCHANGE AND TWO-DIMENSIONAL NMR", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, vol. 249, 17 August 1990 (1990-08-17), pages 755 - 759, XP000938506, ISSN: 0036-8075
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