Peptide Inhibitors of Sodium Channels
AssigneesThe University of North Carolina at Chapel Hill, Spyryx Biosciences, Inc.
InventorsRobert Tarran, Dale J. Christensen
Life of this patent
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Abstract
The present invention relates to the ability of specialized non-naturally occurring peptides to bind to sodium channels and inhibit activation of the sodium channels. The invention further relates to methods for regulating of sodium absorption and fluid volume and treating disorders responsive to modulating sodium absorption by modulating the binding of specialized non-naturally occurring peptides to sodium channels.
Claims42
A peptide comprising the sequence:
- X1-X2-X3-X4-X5-X6-X7-X8 (SEQ ID NO:116)
- wherein:
- X1 is leucine or a conservative substitution with a natural or non-natural amino acid;
- X2 is proline or a conservative substitution with a natural or non-natural amino acid;
- X3 is valine or a conservative substitution with a natural or non-natural amino acid;
- X4 is proline or a conservative substitution with a natural or non-natural amino acid;
- X5 is leucine or a conservative substitution with a natural or non-natural amino acid;
- X6 is aspartic acid or a conservative substitution with a natural or non-natural amino acid;
- X7 is glutamine or a conservative substitution with a natural or non-natural amino acid;
- and
- X8 is threonine or a conservative substitution with a natural or non-natural amino acid;
- or a functional fragment thereof.
A peptide comprising the sequence:
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 (SEQ ID NO:117)
- wherein:
- X1 is leucine, norleucine, or valine;
- X2 is proline, 4-hydroxyproline, (2R,5S)-5-phenyl-pyrrolidine-2-carboxylic acid, or 3,4-dehydro-L-proline;
- X3 is valine, leucine, norleucine, or N-methylvaline;
- X4 is proline, 4-hydroxyproline, (2R,5S)-5-phenyl-pyrrolidine-2-carboxylic acid, or 3,4-dehydro-L-proline;
- X5 is leucine, norleucine, or valine;
- X6 is aspartic acid or glutamic acid;
- X7 is glutamine or asparagine;
- and
- X8 is threonine, serine, or L-α-methylserine;
- or a functional fragment thereof.
A peptide comprising the sequence:
- X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15 (SEQ ID NO:118)
- wherein:
- X1 is leucine or a conservative substitution with a natural or non-natural amino acid;
- X2 is proline or a conservative substitution with a natural or non-natural amino acid;
- X3 is valine or a conservative substitution with a natural or non-natural amino acid;
- X4 is proline or a conservative substitution with a natural or non-natural amino acid;
- X5 is leucine or a conservative substitution with a natural or non-natural amino acid;
- X6 is aspartic acid or a conservative substitution with a natural or non-natural amino acid;
- X7 is glutamine or a conservative substitution with a natural or non-natural amino acid;
- X8 is threonine or a conservative substitution with a natural or non-natural amino acid;
- X9 is threonine or a conservative substitution with a natural or non-natural amino acid;
- X10 is leucine or a conservative substitution with a natural or non-natural amino acid;
- X11 is proline or a conservative substitution with a natural or non-natural amino acid;
- X12 is asparagine or a conservative substitution with a natural or non-natural amino acid;
- X13 is valine or a conservative substitution with a natural or non-natural amino acid;
- X14 is asparagine or a conservative substitution with a natural or non-natural amino acid;
- and
- X15 is proline or a conservative substitution with a natural or non-natural amino acid;
- or a functional fragment thereof.
A peptide comprising the sequence of SEQ ID NO:127 or SEQ ID NO:128.
Dependencies are inferred from the claim text.