RGD-BINDING COMPOUNDS AND METHODS OF USE
First Claim
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1. A pharmaceutical composition for treating conditions associated with metabolic syndrome in a subject in need thereof, comprising a therapeutically effective dose of an RGD-binding compound, or mimetics thereof, comprising a polyphenol conjugated to a polymer.
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Abstract
Provided herein are compositions and methods for preventing and treating diseases and risk factors associated with metabolic syndrome by targeting the RGD-binding site of selected intra- and extracellular proteins. Exemplary compositions include RGD-polyphenol conjugates via an ester linkage; polyphenol polymer conjugated to RGD analogs or mimetics; and RGD polymer conjugates linked to polyphenol.
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Citations
34 Claims
- 1. A pharmaceutical composition for treating conditions associated with metabolic syndrome in a subject in need thereof, comprising a therapeutically effective dose of an RGD-binding compound, or mimetics thereof, comprising a polyphenol conjugated to a polymer.
- 5. A pharmaceutical composition for preventing fat cell differentiation or fat cell accumulation in a subject in need thereof, comprising a therapeutically effective dose of an RGD-binding compound, or mimetics thereof.
- 7. A method of treating conditions associated with metabolic syndrome comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound that binds to one or more intra-cellular lipogenic proteins encoding the amino acid sequence Arg-Gly-Asp.
- 11. A method of treating conditions associated with metabolic syndrome comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a compound that binds to one or more extra-cellular proteins encoding the amino acid sequence Arg-Gly-Asp.
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14. A method for identifying target peptides encoding the amino acid sequence Arg-Gly-Asp, the method comprising:
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(a) providing an affinity column containing at least one compound that binds to the amino acid sequence Arg-Gly-Asp; (b) contacting said target peptides with said at least one compound in said affinity column; and (c) collecting the target peptides that bind to the compounds in the affinity column, wherein the target peptides that bind to the compounds in the affinity column contain a functional RGD-binding site.
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15. A method for identifying genes encoding the amino acid sequence Arg-Gly-Asp that are regulated in opposing directions by insulin and at least one RGD-binding compound, the method comprising:
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(a) selectively stimulating expression of an unknown gene product that encodes the amino acid sequence Arg-Gly-Asp; (b) isolating said gene product from control, resveratrol- and insulin-stimulated cells alone and in combination; (c) pooling said gene products; and (c) analyzing the pools of gene product to identify genes regulated in opposing directions by insulin and at least one RGD-binding compound. - View Dependent Claims (16)
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17. A method of screening for indicators of insulin sensitivity that encode the amino acid sequence Arg-Gly-Asp, the method comprising:
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(a) providing an affinity column containing at least one compound that binds to the amino acid sequence Arg-Gly-Asp; (b) introducing serum collected from a subject exposed to nutritional manipulations, or from a subject afflicted with a condition associated with metabolic syndrome to said column, said serum containing at least one indicator of insulin sensitivity; and (c) collecting at least one indicator that binds to the compounds in the affinity column, wherein an indicator that binds to the compounds in the affinity column encode the amino acid sequence Arg-Gly-Asp and represents an indicator of insulin sensitivity. - View Dependent Claims (18)
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19. A method of screening a test compound for modulating insulin sensitivity, the method comprising:
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(a) providing a cell culture comprising a first cell line overexpressing a recombinant expression construct containing at least one intra-cellular protein encoding the amino acid sequence Arg-Gly-Asp, and a second cell line overexpressing a recombinant expression construct containing at least one mutant derivative of the protein expressed in said first cell line; (b) adding the test compound to the cell culture; (c) assaying the cell culture to determine whether the test compound is taken up by the first and second cell lines; (d) assaying the first and second cell lines to determine whether the test compound binds the protein expressed by the first and second cell line, wherein binding of the test compound to the protein expressed by the first cell line, but not the protein expressed by the second cell line, indicates that the test compound modulates insulin activity. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28)
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- 29. A method for inhibiting the activity or expression of a protein encoding the amino acid sequence Arg-Gly-Asp, the method comprising administering to a subject in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an RGD-binding compound.
Specification