Screening of drugs from chemical combinatorial libraries employing transponders
First Claim
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1. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
- (a) providing a solid phase having a transponder associated with the solid phase and the compound attached to a surface of the solid phase, wherein the transponder comprises of memory elements containing data indicating the identity of the compound, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) providing a fluorescently labeled form of the target biomolecule;
(c) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;
(d) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and
(e) decoding the transponder memory elements to determine the identity of the compound.
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Abstract
Materials and methods are disclosed for identifying chemical compounds having desired binding properties towards a binding partner of pharmaceutical interest. The method employs transponders associated with the solid phase material used in the assay and a scanner to encode and decode data stored electronically on the transponder. The data stored on the transponder identifies the monomeric building blocks added during the synthesis. The structural identification of synthesized compounds bound to the solid phase is done by decoding the transponder.
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Citations
25 Claims
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1. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
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(a) providing a solid phase having a transponder associated with the solid phase and the compound attached to a surface of the solid phase, wherein the transponder comprises of memory elements containing data indicating the identity of the compound, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) providing a fluorescently labeled form of the target biomolecule;
(c) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;
(d) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and
(e) decoding the transponder memory elements to determine the identity of the compound. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
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(a) providing a solid phase having a transponder associated with the solid phase and having a chemical scaffold attached to a surface of the solid phase, the scaffold having active groups, and the transponder comprising of memory elements, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compound;
(c) encoding data on the transponder memory elements to indicate each substituent added;
(d) providing a fluorescently labeled form of the target biomolecule;
(e) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;
(f) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and
(g) decoding the transponder memory elements to determine the identity of the synthesized compound. - View Dependent Claims (9, 10, 11, 12)
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13. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
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(a) providing a solid phase having a transponder associated with the solid phase and having a chemical scaffold attached to a surface of the solid phase, the scaffold having active groups, and the transponder comprising of memory elements containing an unique identifier, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compound;
(c) associating the unique identifier with the identity of the chemical substituents;
(d) providing a fluorescently labeled form of the target biomolecule;
(e) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;
(f) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and
(g) decoding the transponder memory elements to determine the identity of the synthesized compound. - View Dependent Claims (14, 15, 16, 17)
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18. A method of screening compounds for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
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(a) providing a particulate solid phase having a transponder associated with each particle and a chemical scaffold having active groups attached to a surface of the particle, wherein the transponder comprises of memory elements, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) dividing the particles randomly into groups;
(c) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compounds, encoding data on the transponder for each addition to indicate the substituent added, combining the groups and redividing the particles into groups after each addition;
(d) repeating the addition, combining and re-dividing steps until all active groups on the scaffold have been reacted;
(e) providing a fluorescently labeled form of the target biomolecule;
(f) incubating the particles having the synthesized compounds attached thereto with the fluorescently labeled target biomolecule;
(g) analyzing the particles using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compounds; and
(h) decoding the transponder memory elements to determine the identity of the synthesized compounds on the particles analyzed. - View Dependent Claims (19, 20, 21)
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22. A method of screening compounds for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:
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(a) providing a particulate solid phase having a transponder associated with each particle and a chemical scaffold having active groups attached to a surface of the particle, wherein the transponder comprises of memory elements containing an unique identifier, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;
(b) dividing the particles randomly into groups;
(c) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compounds, combining the groups and re-dividing the particles into groups after each addition;
(d) repeating the addition, combining and re-dividing steps until all active groups on the scaffold have been reacted;
(e) associating the unique identifiers with the identity of the chemical substituents;
(f) providing a fluorescently labeled form of the target biomolecule;
(g) incubating the particles having the synthesized compounds attached thereto with the fluorescently labeled target biomolecule;
(h) analyzing the particles using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compounds; and
(i) decoding the unique identifiers in the transponder memory elements to determine the identity of the synthesized compounds on the particle analyzed. - View Dependent Claims (23, 24, 25)
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Specification