G protein coupled receptor agonists and antagonists and methods of activating and inhibiting g protein coupled receptors using the same
AssigneeTufts Medical Center, Inc.
InventorsAthan Kuliopulos, Lidija Covic
Life of this patent
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Abstract
The invention relates generally to G protein coupled receptors and in particular to agonists and antagonists of G protein receptors and methods of using the same.
Claims22
A polypeptide comprising:
- a) a first domain comprising an intracellular loop, or a fragment thereof of a G protein coupled receptor (GPCR), and
- b) a second domain, attached to the first domain, wherein said second domain is a cell-penetrating, membrane-tethering moiety, wherein said polypeptide is a GPCR agonist or antagonist and does not comprise an extracellular portion of the GPCR and said first domain is at least 3 contiguous amino acid residues.
A method of treating a pathology wherein the pathology is related to aberrant expression or aberrant physiological interactions of a GPCR in a subject in need thereof, the method comprising administering to the subject an effective amount of a polypeptide, wherein the polypeptide comprises
- a) a first domain comprising an intracellular loop, or a fragment thereof of a G protein coupled receptor (GPCR), and
- b) a second domain, attached to the first domain, wherein said second domain is a cell-penetrating, membrane-tethering moiety, wherein said polypeptide is a GPCR agonist or antagonist and does not comprise an extracellular portion of the GPCR and said first domain is at least 3 contiguous amino acid residues thereby treating the pathology.
A method for identifying a potential therapeutic agent for use in treatment of a pathology wherein the pathology is related to aberrant expression or aberrant physiological interactions of a GPCR, the method comprising:
- a) providing a cell comprising a GPCR and a property or function ascribable to said GPCR;
- b) contacting the cell with a composition comprising a candidate substance;
- c) contacting the cell with a polypeptide comprising a first domain comprising an intracellular loop or a fragment thereof of a G protein coupled receptor (GPCR), and a second domain, attached to the first domain, wherein said second domain is a naturally or non-naturally occurring cell-penetrating, membrane-tethering moiety, wherein said polypeptide is an agonist or an antagonist of a GPCR, wherein said polypeptide does not comprise an extracellular portion of the GPCR and wherein said first domain is at least 3 contiguous amino acid residues;
- and
- d) determining whether the composition comprising the candidate substance alters the property or function ascribable to said GPCR;
- whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.
Dependencies are inferred from the claim text.