Peptidyl calcineurin inhibitors
Improved calcineurin inhibitors and methods of using these improved calcineurin inhibitors to inhibit calcineurin-NFAT signaling in cells and in subjects are disclosed.
1. A composition, comprising a peptide 7 to 100 amino acids in length comprising the amino acid sequence SEQ ID NO:1, and wherein the composition inhibits calcineurin (CN) —nuclear factor of activated T cell (NFAT) signaling.
2. The composition of claim 1 , wherein the peptide comprises the amino acid sequence SEQ ID NO:2.
3. The composition of claim 1 , wherein the peptide comprises the amino acid sequence SEQ ID NO:3.
4. The composition of claim 1 , wherein the peptide comprises the amino acid sequence SEQ ID NO:4.
5. The composition of claim 1 , wherein the peptide comprises an amino acid sequence selected from the group consisting of SEQ NOs:33-46.
6. The composition of claim 1 , wherein the composition binds to CN with at least about 10-fold higher affinity than SEQ ID NO:47.
7. The composition of claim 1 , having a K D (nM) for CN of about 43±12 or less.
8. The composition of claim 1 , having a K D (nM) for CN of about 2.6±0.8.
9. A method for inhibiting CN-NFAT signaling in a cell, comprising contacting the cell with the composition of claim 1 .