Beta-superfamily conotoxins
AssigneeUniversity of Utah Research Foundation
InventorsRobert M. Jones, Baldomero M. Olivera, Maren Watkins, James E. Garrett
Life of this patent
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Abstract
The present invention is directed to β-superfamily conotoxin peptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated ion channels, ligand gated channels and other receptors. The invention is further directed to nucleic acid sequences encoding the β-superfamily conotoxin peptides and encoding β-superfamily conotoxin propeptides, as well as the β-superfamily conotoxin propeptides.
Claims61
An isolated peptide selected from the group consisting of:
- (a) a peptide selected from the group consisting of peptides comprising amino acid sequences set forth in SEQ ID NOs:3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, 90, 93, 96, 99, 102, 105, 108, 111, 114, 117, 120, 123, 126, 129, 132, 135, 138, 141, 144, 147, 150, 153, 156, 159, 162, 165, 168, 171, 174, 177, 180, 183, 186, 189, 192, 195, 198, 201, 204, 207, 210, 216, 219, 222, 225, 228-287, 289-315, 319-321, 323-337 and 340;
- and
- (b) analogs and derivatives of the peptide in (a).
An isolated nucleic acid encoding a β-superfamily conopeptide propeptide selected from the group of propeptides comprising amino acid sequences set forth in SEQ ID NO:2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 158, 161, 164, 167, 170, 173, 176, 179, 182, 185, 188, 191, 194, 197, 200, 203, 206, 209, 215, 218, 221, 224, and 227.
An isolated β-superfamily conopeptide propeptide selected from the group of propeptides comprising amino acid sequences set forth in SEQ ID NO:2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, 38, 41, 44, 47, 50, 53, 56, 59, 62, 65, 68, 71, 74, 77, 80, 83, 86, 89, 92, 95, 98, 101, 104, 107, 110, 113, 116, 119, 122, 125, 128, 131, 134, 137, 140, 143, 146, 149, 152, 155, 158, 161, 164, 167, 170, 173, 176, 179, 182, 185, 188, 191, 194, 197, 200, 203, 206, 209, 215, 218, 221, 224, and 227.
A method for treating cancer which comprises administering an active agent or a pharmaceutically acceptable salt thereof to an individual having cancer, wherein said active agent is a peptide tagged with a radionuclide, wherein said peptide is a β-superfamily conotoxin.
A method of alleviating pain in an individual which comprises administering to an individual who is either exhibiting pain or is about to be subjected to a pain-causing event a pain-alleviating amount of an active agent or a pharmaceutically acceptible salt thereof, wherein said active agent is a β-superfamily conotoxin.
A method for treating or preventing disorders associated with a disorder selected from the group consisting of voltage-gated ion channel disorders, ligand-gated ion channel disorders and receptor disorders, such as disorders of G-protein coupled receptors, in an individual which comprises administering to an individual in need thereof a therapeutically effective amount of an active agent or a pharmaceutically acceptible salt thereof, wherein the active agent is a β-superfamily conotoxin.
A method for identifying drug candidates for use as treating or preventing disorders associated with a disorder selected from the group consisting of voltage-gated ion channel disorders, ligand-gated ion channel disorders and receptor disorders, such as disorders of G-protein coupled receptors which comprises screening a drug candidate for its action at or partially at the same functional site as a β-superfamily conotoxin and capable of elucidation of similar functional response as said conotoxin.
A method of identifying compounds that mimic the therapeutic activity of a β-superfamily conotoxin, comprising the steps of:
- (a) conducting a biological assay on a test compound to determine the therapeutic activity;
- and (b) comparing the results obtained from the biological assay of the test compound to the results obtained from the biological assay of a β-superfamily conotoxin.
A method for designing a β-beta turn mimetic of a β-superfamily conotoxin containing a β-turn motif selected from the group consistinf of (i) a -CX1X2KX1C- (SEQ ID NO:338) motif, wherein X1 is any amino acid and X2 is D or L Trp or D or L 6-bromo Trp and (ii) a -CPX3RVC- (SEQ ID NO:339) motif, wherein X3 is D or L Phe, which comprises replacing this motif with a non-peptide turn mimetic β-turn scaffold and then attaching receptor binding domains contained within the N and C-terminal sequences of a β-superfamily conotoxin to the β-turn scaffold to mimic the 3D spatial array within the native β-superfamily conotoxin.
Dependencies are inferred from the claim text.