Compositions and methods for detecting and treating diseases and conditions related to chemokine receptors
First Claim
1. A method of identifying an agent that binds to a chemokine receptor having a first topology but does not bind to a chemokine receptor having a second topology, the method comprising,i. providing a first cell comprising the chemokine receptor having the first topology and a second cell comprising the chemokine receptor having the second topology, wherein the chemokine receptor is selected from the group consisting of CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR5, CXCR6, CX3CR1, CXR1, CCXCKR (CCR11), US28, ECRF3, Kaposi'"'"'s Sarcoma-associated Herpesvirus GPCR, Poxvirus membrane-bound G Protein-coupled receptors, D6, and DARC.ii. contacting an agent to the chemokine receptor;
- andiii. selecting an agent that binds to the chemokine receptor having the first topology, but does not bind to the chemokine receptor having the second topology, wherein the chemokine receptor having the first topology and the chemokine receptor having the second topology have the same amino acid sequence.
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Abstract
The present invention provides methods for identifying an agent that specifically binds and/or modulates one topology of chemokine receptor but not a second topology of the receptor. Such agents are useful as therapeutics for diseases or conditions associated with a particular chemokine receptor topology. Moreover, the agents are useful for detecting a particular topology of a chemokine receptor, thereby diagnosing disease or predisposition for a disease. In addition, the agents are useful for identifying and isolating cells that express a particular topology of a chemokine receptor.
28 Citations
22 Claims
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1. A method of identifying an agent that binds to a chemokine receptor having a first topology but does not bind to a chemokine receptor having a second topology, the method comprising,
i. providing a first cell comprising the chemokine receptor having the first topology and a second cell comprising the chemokine receptor having the second topology, wherein the chemokine receptor is selected from the group consisting of CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR5, CXCR6, CX3CR1, CXR1, CCXCKR (CCR11), US28, ECRF3, Kaposi'"'"'s Sarcoma-associated Herpesvirus GPCR, Poxvirus membrane-bound G Protein-coupled receptors, D6, and DARC. ii. contacting an agent to the chemokine receptor; - and
iii. selecting an agent that binds to the chemokine receptor having the first topology, but does not bind to the chemokine receptor having the second topology, wherein the chemokine receptor having the first topology and the chemokine receptor having the second topology have the same amino acid sequence. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A method of identifying novel topologies of a chemokine receptor the method comprising;
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providing a cell type and a second cell type, each cell type expressing a chemokine receptor selected from the group consisting of CCR1, CCR2, CCR3, CCR4, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CX3CR1, CXR1, CCXCKR (CCR11), US28, ECRF3, Kaposi'"'"'s Sarcoma-associated Herpesvirus GPCR, Poxvirus membrane-bound G Protein-coupled receptors, D6, and DARC; testing a plurality of different chemokines for the ability to bind to the chemokine receptor on the two cell types; and identifying a chemokine, wherein the chemokine binds to the chemokine receptor on the first cell type, but does not bind to the chemokine receptor on the second cell type, thereby identifying novel topologies of the chemokine receptor. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification