Method for detecting macromolecular conformational change and binding information
AssigneeThe Regents of the University of California
InventorsAlexander Pines, David E. Wemmer, Megan Spence, Seth Rubin, E. Janette Ruiz, Ivan E. Dimitrov
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Abstract
An active-nucleus sensor or a functionalized active-nucleus complex sensor is utilized in a method for detecting conformational change and binding event information in a targeted molecule, wherein the sensor does not participate in the conformational change or binding event. The method directly or indirectly detects the occurrence, deletion, shift, or any measurable change in a magnetic resonance signal with a unique magnetic resonance property from the active-nuclei, frequently hyperpolarized 129Xe.
Claims49
A method for detecting a conformational change or binding event in a targeted molecule, comprising:
- (a) producing a magnetically active-nucleus sensor capable of producing a detectable signal when the targeted molecule undergoes a conformational change or binding event;
- (b) combining said magnetically active-nucleus sensor with said targeted molecule;
- and
- (c) recording said detectable signal upon said conformational change or binding event, wherein said sensor does not participate in the conformational change or binding event.
A method for detecting a conformational change in a targeted macromolecule, comprising:
- (a) producing a magnetically active-nucleus sensor capable of producing a detectable signal when the targeted macromolecule undergoes a conformational change;
- (b) combining said magnetically active-nucleus sensor with said targeted macromolecule;
- and
- (c) recording said detectable signal upon said conformational change, wherein said sensor does not participate in the conformational change.
A method for detecting binding of a ligand to a targeted macromolecule, wherein the ligand binding produces a detectable conformational change in the targeted macromolecule or a detectable binding event, comprising:
- (a) producing a magnetically active-nucleus sensor capable of producing a detectable signal when the targeted macromolecule undergoes a ligand-induced conformational change or upon the binding event;
- (b) combining said magnetically active-nucleus sensor with said targeted macromolecule;
- and
- (c) recording said detectable signal upon said ligand-induced conformational change or binding event, wherein said sensor does not participate in the conformational change or binding event.
A method for detecting a conformational change induced by a binding event in a targeted macromolecule, comprising:
- (a) producing a magnetically active-nucleus sensor capable of producing a detectable signal when the targeted macromolecule undergoes the binding event induced conformational change;
- (b) combining said magnetically active-nucleus sensor with said targeted macromolecule;
- and
- (c) recording said detectable signal upon said binding event induced conformational change, wherein said sensor does not participate in the conformational change.
A method for detecting a binding event or environmental alteration induced conformational change in a targeted macromolecule, comprising:
- (a) producing a magnetically active-nucleus sensor capable of producing a detectable signal when the targeted macromolecule undergoes the conformational change;
- (b) combining said magnetically active-nucleus sensor with said targeted macromolecule;
- and
- (c) recording said detectable signal upon said conformational change, wherein said sensor does not participate in the conformational change or binding event.
A method for detecting a conformational change or a binding event in a targeted protein, comprising:
- (a) producing a hyperpolarized 129Xe sensor;
- (b) combining said hyperpolarized 129Xe sensor with said targeted protein;
- and
- (c) recording from said hyperpolarized 129Xe sensor an NMR and/or MRI detectable signal upon said conformational change or binding event, wherein said 129Xe sensor does not participate in the conformational change or binding event.
A method for detecting a binding event or environmental alteration induced conformational change or binding event in a targeted protein, comprising:
- (a) producing a hyperpolarized 129Xe sensor;
- (b) combining said hyperpolarized 129Xe sensor with said targeted protein;
- and
- (c) recording from said hyperpolarized 129Xe sensor an NMR and/or MRI detectable signal upon said conformational change or binding event, wherein said 129Xe sensor does not participate in the conformational change or binding event.
A method for detecting a conformational change or binding event in a targeted macromolecule, comprising:
- (a) functionalizing a magnetically active nucleus by incorporating said nucleus into a macromolecular or molecular complex that is capable of binding the targeted macromolecule;
- (b) bringing said macromolecular or molecular complex into contact with the targeted macromolecular;
- and
- (c) detecting the occurrence, deletion, or change in a nuclear magnetic resonance signal from said functionalized nucleus in order to detect any conformational change in the targeted macromolecule or binding event, wherein said complex does not participate in the conformational change or binding event.
A method for detecting conformational changes in a plurality of targeted macromolecules or binding events utilizing a plurality of functionalized active-nucleus sensor complexes with at least two of the functionalized active-nucleus sensor complexes having an attraction affinity to different corresponding targeted macromolecules, comprising:
- (a) for each functionalized active-nucleus complex, functionalizing an active-nucleus by incorporating said active-nucleus into a macromolecular or molecular sensor complex that is capable of binding one of said targeted macromolecules;
- (b) bringing said macromolecular or molecular sensor complexes into contact with the targeted macromolecules;
- and
- (c) detecting the occurrence of or change in a nuclear magnetic resonance signal from each of said active-nuclei in each of said functionalized active-nucleus sensor complexes in order to detect conformational changes in the targeted macromolecules or binding event, wherein said complexes do not participate in the conformational change or binding event.
Dependencies are inferred from the claim text.