US2017218040A1PendingUtilityA1

Proteolically resistant cyclotides with angiotensin 1-7 like activity

35
Assignee: CAMARERO PALAO JULIO APriority: Feb 2, 2016Filed: Feb 1, 2017Published: Aug 3, 2017
Est. expiryFeb 2, 2036(~9.5 yrs left)· nominal 20-yr term from priority
Inventors:Julio A. Camarero PalaoTeshome L. AboyeKathleen E. Rodgers
C07K 14/575C07K 14/001
35
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

Described herein is a novel cyclotide able to activate the unique receptor of angiotensin-(1-7) (AT1-7), the MAS1 receptor. This cyclotide may be used in the treatment of cancer and myocardial infarction.

Claims

exact text as granted — not AI-modified
1 . A cyclotide comprising a cyclotide backbone and a peptide comprising an angiotensin polypeptide or an equivalent thereof. 
     
     
         2 . The cyclotide of  claim 1 , wherein the angiotensin polypeptide comprises a polypeptide of the group of an angiotensin1-1-7 polypeptide, an angiotensin 1-4 polypeptide, or an angiotensin 1-5 polypeptide, or an equivalent of each thereof. 
     
     
         3 . The cyclotide of  claim 1 , wherein the angiotensin polypeptide is from the group of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 (XRV Y IE), wherein X is the amino acid L-2,3-diaminopropionic acid, SEQ ID NO: 14 (XRVYIHE), wherein X is the amino acid L-2,3-diaminopropionic acid, SEQ ID NO: 15, SEQ ID NO: 16, or an equivalent of each thereof. 
     
     
         4 . A cyclotide of  claim 1 , wherein the cyclotide is from the group of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, or an equivalent of each thereof, wherein the equivalent comprises a polypeptide that maintains a cystine-knot scaffold and head-to-tail cyclization but in which hypermutation of essentially all residues is permitted with the exception of the strictly conserved cysteines that comprise the knot. 
     
     
         5 . The cyclotide of  claim 1 , wherein the cyclotide backbone is a polypeptide from the group of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or an equivalent of each thereof, wherein the equivalent comprises a polypeptide that maintains a cystine-knot scaffold and head-to-tail cyclization but in which hypermutation of essentially all residues is permitted with the exception of the strictly conserved cysteines that comprise the knot. 
     
     
         6 . The cyclotide of  claim 1 , wherein the cyclotide backbone is a polypeptide from the group of SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 271, SEQ ID NO: 272, SEQ ID NO: 273, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, SEQ ID NO: 278, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 300, or an equivalent of each thereof, wherein the equivalent comprises a polypeptide that maintains a cystine-knot scaffold and head-to-tail cyclization but in which hypermutation of essentially all residues is permitted with the exception of the strictly conserved cysteines that comprise the knot. 
     
     
         7 . The cyclotide of  claim 1 , further comprising a label or purification marker. 
     
     
         8 . The cyclotide of  claim 1 , further comprising a carrier. 
     
     
         9 . A plurality of cyclotides of  claim 1 . 
     
     
         10 . The plurality of  claim 9 , wherein the amino acid sequences of the plurality are the same or different from each other. 
     
     
         11 . The cyclotide of  claim 8 , wherein the carrier is a pharmaceutically acceptable carrier. 
     
     
         12 . The plurality of  claim 10 , further comprising a carrier. 
     
     
         13 . The plurality of  claim 12 , wherein the carrier is a pharmaceutically acceptable carrier. 
     
     
         14 . The cyclotide of  claim 11 , wherein the pharmaceutically acceptable carrier further comprises a therapeutic agent. 
     
     
         15 . The plurality of  claim 12 , wherein the pharmaceutically acceptable carrier further comprises a therapeutic agent. 
     
     
         16 . An isolated polynucleotide encoding the cyclotide of  claim 1 , or an equivalent of each thereof. 
     
     
         17 . A complement of the polynucleotide of  claim 16 . 
     
     
         18 . An isolated polynucleotide of  claim 17 , further comprising a label or a purification marker. 
     
     
         19 . An isolated polynucleotide of  claim 16 , and a carrier. 
     
     
         20 . The isolated polynucleotide of  claim 19 , wherein the carrier is a pharmaceutically acceptable carrier. 
     
     
         21 . A vector comprising the isolated polynucleotide of  claim 16 . 
     
     
         22 . An isolated host cell comprising the cyclotide of  claim 1 . 
     
     
         23 . The isolated host cell of  claim 22 , wherein the cell is a eukaryotic cell or a prokaryotic cell. 
     
     
         24 . An isolated host cell comprising the polynucleotide of  claim 16 . 
     
     
         25 . The isolated host cell of  claim 24 , wherein the isolated host cell is a eukaryotic cell or a prokaryotic cell. 
     
     
         26 . The isolated host cell of  claim 25 , wherein the cell is a prokaryotic cell. 
     
     
         27 . A method for producing a recombinant cyclotide polypeptide, comprising growing the isolated host cell of  claim 24 , under conditions to express the polynucleotide. 
     
     
         28 . The method of  claim 27 , further comprising purifying the polypeptide. 
     
     
         29 . A method for any one of: promoting vasodilation in a tissue, inhibiting the proliferation of a cell or tissue, or inhibiting angiogenesis, comprising contacting the cell or tissue with a cyclotide of  claim 1 . 
     
     
         30 . The method of  claim 29 , wherein the cell or tissue is a mammalian cell or tissue. 
     
     
         31 . The method of  claim 30 , wherein the mammalian cell or tissue is a human cell or tissue. 
     
     
         32 . The method of  29 , wherein the contacting is in vitro or in vivo. 
     
     
         33 . A method for inhibiting the growth of a tumor cell comprising contacting the tumor cell with a cyclotide of  claim 1 . 
     
     
         34 . The method of  claim 33 , wherein the tumor cell expresses MAS1. 
     
     
         35 . The method of  claim 33 , wherein the tumor cell is a lung cancer tumor cell or a breast cancer tumor cell. 
     
     
         36 . The method of  claim 33 , wherein the tumor cell is mammalian cell. 
     
     
         37 . The method of  claim 36 , wherein the mammalian cell is a human cell. 
     
     
         38 . The method of  claim 33 , wherein the contacting is in vitro or in vivo. 
     
     
         39 . A method for any one of: promoting vasodilation in a tissue, inhibiting the proliferation of a cell or tissue, treating myocardial infarction or inhibiting angiogenesis, in a subject in need thereof, comprising administering to a subject in need thereof, an effective amount of cyclotide of  claim 1 . 
     
     
         40 . A method for inhibiting the growth of a tumor in a subject in need thereof, comprising administering to the subject an effective amount of the cyclotide of  claim 1 . 
     
     
         41 . The method of  claim 40 , wherein the tumor expresses MAS1. 
     
     
         42 . The method of  claim 41 , wherein the tumor is a lung cancer tumor or breast cancer tumor. 
     
     
         43 . The method of  claim 40 , wherein the subject is a mammal. 
     
     
         44 . The method of  claim 40 , wherein the subject is a human.

Join the waitlist — get patent alerts

Track US2017218040A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.