Method for applying NMR for ligand discovery or as a drug screening tool
AssigneeUniversiteit Leiden
InventorGregg David Siegal
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Abstract
The present invention relates to a method for screening compounds to identify compounds that bind to a specific target, comprising the steps of: (a) providing a target immobilized to a solid support; (b) generating a first NMR spectrum of the said compounds to be screened in the presence of the solid support without the target molecule immobilized thereto; (c) generating a second NMR spectrum of the said compounds to be screened in the presence of the solid support with the target molecule immobilized thereto; and (d) comparing said first and second NMR spectrum to determine differences between said first and second NMR spectrum. Further the invention relates to an NMR apparatus having arranged therein a particular NMR probe.
Claims11
An NMR apparatus comprising an NMR probe suitable for flow-through NMR screening of a test sample,
- wherein said apparatus comprises a probe;
- wherein said probe comprises a first vessel and a second vessel;
- wherein the first vessel and second vessel are connected to a flow inlet and a flow outlet,
- wherein both vessels contain a solid support;
- wherein the solid support comprises a polymer,
- wherein only one of said solid supports has a target immobilized thereto;
- wherein said target is reusable in situ;
- wherein said probe comprises only one detection coil which is arranged around said first and second vessels;
- and
- wherein the apparatus comprises a first means for generating a pulsed-radio field which at least extends into the first and second vessels of the sample holder, and wherein the apparatus comprises a second means consisting of one or more gradient coils suitably arranged to deliver a pulsed radio field with a linear amplitude gradient along a transverse axis to the first and second vessels.
A method for identifying compounds that bind to a specific target, the method comprising:
- (a) pumping a sample of interest into a an NMR apparatus, wherein the NMR apparatus comprises a probe;
- wherein said probe comprises a first sample vessel and a second sample vessel;
- wherein both sample vessels contain a solid support, wherein the solid support is a polymer;
- wherein only one of said solid supports has a target immobilized thereto, and wherein the sample is pumped into said sample vessels,
- (b) stopping said flow when the sample of interest reaches the first and second sample vessels;
- (c) generating NMR spectra of the sample of interest from the first and second vessels;
- (d) pumping the sample out of the vessels and through the NMR apparatus via a flow outlet;
- (e) reusing said target in situ, and
- (f) analyzing and comparing said NMR spectra to determine differences between said spectra,
- wherein the sample of interest comprises a solution in which one or more compounds being identified for binding are dissolved;
- wherein said first and second spectra are detected at about the same time using the same solution;
- and
- wherein said probe comprises only one detection coil which is arranged around said sample vessels.
Dependencies are inferred from the claim text.