BK channel-modulating peptides and their use
View Patent ↗The present invention concerns peptides and nucleic acids encoding the peptides, and their use for modulating large conductance Ca 2+ 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.
1. An isolated peptide comprising an amino acid sequence selected from among: CARGVYRVC (SEQ ID NO:1), CRRGLVQVC (SEQ ID NO:3), and CLQEQRGVC (SEQ ID NO. 11).
2. The isolated peptide of claim 1 , wherein the peptide comprises CARGVYRVC (SEQ ID NO: 1), CRRGLVQVC (SEQ ID NO:3), and CLQEQRGVC (SEQ ID NO: 11); and wherein the peptide includes no further amino acid residues.
3. The isolated peptide of claim 1 , wherein the peptide consists of CARGVYRVC (SEQ ID NO: 1), or CRRGLVQVC (SEQ ID NO:3), or CLQEQRGVC (SEQ ID NO: 11).
4. The isolated peptide of claim 1 , wherein the peptide is a circular peptide.
5. The isolated peptide of claim 4 , wherein the peptide has a disulfide bridge between cysteines.
6. The isolated peptide of claim 1 , further comprising a heterologous amino acid sequence, or other moiety, fused directly or indirectly to the amino acid sequence.
7. The isolated peptide of claim 6 , wherein the moiety comprises a detectable label.
8. The isolated peptide of claim 1 , wherein the peptide comprises CARGVYRVC (SEQ ID NO:1).
9. The isolated peptide of claim 1 , wherein the peptide comprises CRRGLVQVC (SEQ ID NO:3).
10. The isolated peptide of claim 1 , wherein the peptide comprises CLQEQRGVC (SEQ ID NO:11).
11. The isolated peptide of claim 1 , wherein the peptide comprises CARGVYRVC (SEQ ID NO: 1), and wherein the peptide includes no further amino acid residues.
12. The isolated peptide of claim 1 , wherein the peptide comprises CRRGLVQVC (SEQ ID NO:3), and wherein the peptide includes no further amino acid residues.
13. The isolated peptide of claim 1 , wherein the peptide comprises CLQEQRGVC (SEQ ID NO: 11), and wherein the peptide includes no further amino acid residues.
14. The isolated peptide of claim 1 , wherein the peptide consists of CARGVYRVC (SEQ ID NO:1).
15. The isolated peptide of claim 1 , wherein the peptide consists of CRRGLVQVC (SEQ ID NO:3).
16. The isolated peptide of claim 1 , wherein the peptide consists of CLQEQRGVC (SEQ ID NO:11).
17. A pharmaceutical composition comprising an isolated peptide; and a pharmaceutically acceptable carrier or diluent, wherein the isolated peptide comprises an amino acid sequence selected from among: CARGVYRVC (SEQ ID NO:1), CRRGLVQVC (SEQ ID NO:3), and CLQEQRGVC (SEQ ID NO: 11).
18. The pharmaceutical composition of claim 17 , wherein the composition comprises a combination of two or all three peptides comprising CARGVYRVC (SEQ ID NO:1), CRRGLVQVC (SEQ ID NO:3), and CLQEQRGVC (SEQ ID NO: 11).
19. The pharmaceutical composition of claim 17 , wherein the composition is a liquid.
20. The pharmaceutical composition of claim 17 , wherein the composition is a solid or semi-solid.