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.
Claims102
A composition comprising a polypeptide, said polypeptide comprising an isolated fragment of a G-protein coupled receptor (GPCR);
- and a non-peptidic cell penetrating moiety linked to said polypeptide.
A composition comprising a polypeptide, said polypeptide comprising an isolated fragment of a G-protein coupled receptor (GPCR);
- and a non-peptidic membrane-tethering moiety linked to said polypeptide.
A composition comprising a polypeptide, said polypeptide comprising an isolated intracellular fragment of a G-protein coupled receptor (GPCR) or an isolated extracellular fragment of a G-protein coupled receptor (GPCR);
- and a cell penetrating moiety linked to said polypeptide.
A composition comprising a polypeptide, said polypeptide comprising an isolated intracellular fragment of a G-protein coupled receptor (GPCR) or an isolated extracellular fragment of a G-protein coupled receptor (GPCR);
- and a membrane-tethering moiety linked to said polypeptide.
A composition comprising a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOS:1-16, SEQ ID NOS:27-29, and SEQ ID NOS 33-36 and a cell penetrating moiety linked to said polypeptide.
A composition comprising a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOS:1-16, SEQ ID NOS:27-29, and SEQ ID NOS 33-36 and a membrane tethering moiety linked to said polypeptide.
A composition according to Formula I:
- A-X-B-Yn (I),
- wherein A is a cell penetrating moiety or a membrane tethering moiety;
- X is a linking moiety;
- B is an isolated intracellular of an isolated extracellular fragment of a G-protein coupled receptor (GPCR);
- Y is a hydrophobic peptide, amino acid, modified amino acid, aromatic moiety, or a lipid,
- and n is zero or one.
An inhibitor of platelet activation, comprising a polypeptide comprising an isolated platelet-inhibitory fragment of a protease activated receptor and a cell penetrating moiety linked to said polypeptide.
A method of inhibiting platelet aggregation, comprising contacting a platelet with a composition comprising an isolated fragment of a protease activated receptor linked to a cell penetrating moiety.
A method of inhibiting thrombus formation in a mammal, comprising administering to said mammal a composition comprising an isolated fragment of a thrombin receptor linked to a cell penetrating moiety.
A vascular endoprosthetic device, comprising an inhibitor of thrombus formation, said inhibitor comprising an isolated fragment of a thrombin receptor linked to a cell penetrating moiety.
A method of inhibiting migration or invasion of a tumor cell, comprising contacting said tumor cell with an isolated fragment of a protease activated receptor linked to a cell penetrating moiety.
A method of inhibiting metastases of a tumor cell, comprising contacting said tumor cell with an isolated fragment of a protease activated receptor linked to a cell-penetrating moiety.
A method of inhibiting asthma in a subject, comprising administering to said subject a composition comprising an isolated fragment of a thrombin or trypsin/tryptase GPCR linked to a cell penetrating moiety.
An inhibitor of platelet activation, comprising a polypeptide comprising an isolated fragment of a nucleotide GPCR and a cell penetrating moiety linked to said polypeptide.
A method of inhibiting platelet aggregation, comprising contacting a platelet with a composition comprising an isolated fragment of a nucleotide receptor linked to a cell penetrating moiety.
A method of inhibiting thrombus formation in a mammal, comprising administering to said mammal a composition comprising an isolated fragment of a P2Y12 receptor linked to a cell penetrating moiety.
A vascular endoprosthetic device, comprising an inhibitor of thrombus formation, said inhibitor comprising an isolated fragment of a nucleotide receptor linked to a cell penetrating moiety.
A soluble chimeric polypeptide comprising:
- a first domain comprising an extracellular or an intracellular fragment of a GPCR;
- and a second domain comprising a cell-penetrating or a membrane-tethering moiety, linked to said first domain, wherein said second domain comprises a naturally occurring contiguous amino acid from a transmembrane domain adjacent to said extracellular or intracellular fragment, wherein said transmembrane domain is not transmembrane domain 1-7 of the CXCR4, transmembrane domain 1-7 of the CCKA receptor, or transmembrane 2 of the CCR5 receptor.
A soluble chimeric polypeptide comprising:
- a first domain comprising an extracellular or an intracellular fragment of a GPCR;
- and a second domain comprising a cell-penetrating or a membrane-tethering moiety, linked to said first domain, wherein said second domain comprises 1-15 contiguous amino acids of a naturally-occurring transmembrane helix domain adjacent to said extracellular or intracellular fragment.
Dependencies are inferred from the claim text.