Cell-permeable peptide inhibitors of the JNK signal transduction pathway
AssigneeXigen Inflammation Ltd.
InventorChristophe Bonny
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Abstract
Protein kinase inhibitors and more specifically inhibitors of the protein kinase c-Jun amino terminal kinase are described. Additionally, JNK inhibitor sequences, chimeric peptides, nucleic acids encoding same as well as pharmaceutical compositions for treating pathophysiologies associated with JNK signaling are described.
Claims21
A JNK inhibitor sequence consisting of a D-enantiomeric amino acid sequence of SEQ ID NO:
- 2.
A chimeric peptide consisting of a first domain and a second domain linked by a covalent bond, the first domain comprising a trafficking sequence, and the second domain consisting of a JNK inhibitor sequence according to SEQ ID NO:
- 2,
- wherein the trafficking sequence comprises the D-enantiomeric amino acid sequence of SEQ ID NO:
- 5, 6, 7 or 8 or a sequence sharing at least about 90% sequence identity with the D-enantiomeric SEQ ID NOs:
- 5 or 6.
A chimeric peptide consisting of a first domain and a second domain linked by a covalent bond, the first domain comprising a trafficking sequence, and the second domain consisting of a JNK inhibitor sequence,
- wherein the trafficking sequence comprises the D-enantiomeric amino acid sequence of SEQ ID NO:
- 5, 6, 7 or 8 or a sequence sharing at least about 90% sequence identity with the D-enantiomeric SEQ ID NOs:
- 5 or 6, and wherein the JNK inhibitor sequence consists of the D retro inverso amino acid sequence according to NH2-Xnb-DQXXXXXXXLXLTTPR-Xna-Xnb-COOH (SEQ ID NO:
- 4), wherein n for Xna in SEQ ID NO:
- 4 is 0 each Xnb is selected independently, Xnb may not comprise a serine or threonine residue at its C-terminus, and when n for Xnb in SEQ ID NO:
- 4 is 1, Xnb may not be a serine or threonine residue.
Dependencies are inferred from the claim text.