US2022194987A1PendingUtilityA1

Bk channel-modulating peptides and their use

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Assignee: UNIV SOUTH FLORIDAPriority: Jul 14, 2016Filed: Jan 4, 2022Published: Jun 23, 2022
Est. expiryJul 14, 2036(~10 yrs left)· nominal 20-yr term from priority
Inventors:Luisa Lynn ScottJoseph Paul Walton
C07K 7/06A61K 38/08A61K 38/12A61P 27/16C07K 7/54A61K 38/00A61K 47/64A61P 43/00
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Claims

Abstract

The present invention concerns peptides and nucleic acids encoding the peptides, and their use for modulating large conductance Ca2+ activated K+ (BK) channel activity in cells; for treating conditions such as presbycusis (age-related hearing loss), audiogenic seizures, alcohol addiction, cancer, and neurodegenerative disease; and for delivering a cargo moiety to the brain of a subject through the blood-brain barrier.

Claims

exact text as granted — not AI-modified
We claim: 
     
         1 . A composition of matter selected from:
 (a) a peptide comprising an amino acid sequence selected from among: CARGVYRVC (SEQ ID NO:1), CRVAHRAVC (SEQ ID NO:2), CRRGLVQVC (SEQ ID NO:3), CPPGRGAVC (SEQ ID NO:4), CGMTKRPVC (SEQ ID NO:5), CWKSRWYVC (SEQ ID NO:6), CERRMYRVC (SEQ ID NO:7), CRRAYEMVC (SEQ ID NO:8), CRRKRHAVC (SEQ ID NO:9), CAVGRLAVC (SEQ ID NO:10), CLQEQRGVC (SEQ ID NO:11), CRKQGRRVC (SEQ ID NO:12), CEGRRARVC (SEQ ID NO:13). CLDGKLDVC (SEQ ID NO:14), CGGGGSRVC (SEQ ID NO:15), CFTGGGGVC (SEQ ID NO:16), CVWVKRNVC (SEQ ID NO:17), CGMASSFVC (SEQ ID NO:18), CDTMEQRVC (SEQ ID NO:19), CGQQSPGVC (SEQ ID NO:20), CDEMNWWVC (SEQ ID NO:21), CTQAETRVC (SEQ ID NO:22), CPKPNNTVC (SEQ ID NO:23), CVRAPPSVC (SEQ ID NO:24), CQAREVLVC (SEQ ID NO:25), CSEWPQNVC (SEQ ID NO:26), or a functional fragment or variant of any of the foregoing; or   (b) a nucleic acid encoding the peptide of (a); or   (c) an expression vector comprising the nucleic acid of (b); or   (d) a composition comprising the peptide of (a), nucleic acid of (b), or expression vector of (c); and a pharmaceutically acceptable carrier or diluent.   
     
     
         2 . The composition of matter of  claim 1 , wherein the peptide comprises CRRGLVQVC (SEQ ID NO:3). 
     
     
         3 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence consisting of CRRGLVQVC (SEQ ID NO:3). 
     
     
         4 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence comprising the formula CXXXXXXVC (SEQ ID NO:27), wherein X is any natural or non-natural amino acid. 
     
     
         5 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence consisting of the formula CXXXXXXVC (SEQ ID NO:27), wherein X is any natural or non-natural amino acid. 
     
     
         6 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence comprising any one of SEQ ID Nos:28-61, wherein X is any natural or non-natural amino acid. 
     
     
         7 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence consisting of any one of SEQ ID Nos28-61, wherein X is any natural or non-natural amino acid. 
     
     
         8 . The composition of matter of  claim 1 , wherein the peptide consists of an amino acid sequence consisting of any one of SEQ ID Nos28-61, wherein X is any natural or non-natural amino acid. 
     
     
         9 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence selected from among: CARGVYRVC (SEQ ID NO:1), CRVAHRAVC (SEQ ID NO:2), CRRGLVQVC (SEQ ID NO:3), CPPGRGAVC (SEQ ID NO:4), CGMTKRPVC (SEQ ID NO:5), CWKSRWYVC (SEQ ID NO:6), CERRMYRVC (SEQ ID NO:7), CRRAYEMVC (SEQ ID NO:8), CRRKRHAVC (SEQ ID NO:9), CAVGRLAVC (SEQ ID NO:10), CLQEQRGVC (SEQ ID NO:11), CRKQGRRVC (SEQ ID NO:12), CEGRRARVC (SEQ ID NO:13). CLDGKLDVC (SEQ ID NO:14), CGGGGSRVC (SEQ ID NO:15), CFTGGGGVC (SEQ ID NO:16), CVWVKRNVC (SEQ ID NO:17), CGMASSFVC (SEQ ID NO:18), CDTMEQRVC (SEQ ID NO:19), CGQQSPGVC (SEQ ID NO:20), CDEMNWWVC (SEQ ID NO:21), CTQAETRVC (SEQ ID NO:22), CPKPNNTVC (SEQ ID NO:23), CVRAPPSVC (SEQ ID NO:24), CQAREVLVC (SEQ ID NO:25), and CSEWPQNVC (SEQ ID NO:26). 
     
     
         10 . The composition of matter of  claim 1 , wherein the peptide comprises an amino acid sequence consisting of: CARGVYRVC (SEQ ID NO:1), CRVAHRAVC (SEQ ID NO:2), CRRGLVQVC (SEQ ID NO:3), CPPGRGAVC (SEQ ID NO:4), CGMTKRPVC (SEQ ID NO:5), CWKSRWYVC (SEQ ID NO:6), CERRMYRVC (SEQ ID NO:7), CRRAYEMVC (SEQ ID NO:8), CRRKRHAVC (SEQ ID NO:9), CAVGRLAVC (SEQ ID NO:10), CLQEQRGVC (SEQ ID NO:11), CRKQGRRVC (SEQ ID NO:12), CEGRRARVC (SEQ ID NO:13). CLDGKLDVC (SEQ ID NO:14), CGGGGSRVC (SEQ ID NO:15), CFTGGGGVC (SEQ ID NO:16), CVWVKRNVC (SEQ ID NO:17), CGMASSFVC (SEQ ID NO:18), CDTMEQRVC (SEQ ID NO:19), CGQQSPGVC (SEQ ID NO:20), CDEMNWWVC (SEQ ID NO:21), CTQAETRVC (SEQ ID NO:22), CPKPNNTVC (SEQ ID NO:23), CVRAPPSVC (SEQ ID NO:24), CQAREVLVC (SEQ ID NO:25), or CSEWPQNVC (SEQ ID NO:26). 
     
     
         11 . The composition of matter of  claim 1 , wherein the peptide is a circular peptide. 
     
     
         12 . The composition of matter of  claim 11 , wherein the peptide has a disulfide bridge between cysteines. 
     
     
         13 . The composition of matter of  claim 1 , further comprising a heterologous amino acid sequence, or other moiety, fused directly or indirectly to the amino acid sequence. 
     
     
         14 . The composition of matter of  claim 13 , wherein the moiety comprises a detectable label. 
     
     
         15 . A method for treating a condition in a subject in need thereof, comprising administering an agent to the subject, wherein the agent comprises a peptide of  claim 1 , or a nucleic acid encoding the peptide, or an expression construct comprising the nucleic acid; and wherein the condition is selected from among presbycusis, audiogenic seizures, alcohol addiction, cancer, and neurodegenerative disease. 
     
     
         16 . The method of  claim 15 , wherein the subject has the condition at the time of said administering, and the agent is administered to the subject as therapy. 
     
     
         17 . The method of  claim 16 , wherein the agent is administered to the subject by a route selected from the group consisting of intravascular, intramuscular, subcutaneous, oral, intranasal, intra-ocular, topical, and transdermal. 
     
     
         18 . The method of  claim 17 , wherein the subject is a human. 
     
     
         19 . A method selected from:
 (a) a method modulating large conductance Ca 2+  activated K +  (BK) channel activity in a cell having a BK channel in vitro or in vivo, comprising contacting the cell in vitro or in vivo with an agent that comprises a peptide of  claim 1 , or a nucleic acid encoding the peptide, or an expression construct comprising the nucleic acid; or   (b) a method of delivering a cargo moiety to the brain of a subject, through the blood-brain barrier (BBB), comprising administering a polypeptide construct to the subject, wherein the polypeptide construct comprises a peptide of  claim 1  conjugated to the cargo moiety.   
     
     
         20 . The method of  claim 19 , wherein the cargo moiety comprises a detectable label.

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