Peptide that inhibits janus kinase
The present invention provides a method of selecting or designing a compound for the ability to regulate JAK activity. The method comprises assessing the ability of the compound to modulate the interaction of the pseudo-substrate loop (PSL) with the kinase like domain (KLD) of JAK. In addition the present invention provides compounds which inhibit JAK and methods of treatment of JAK-associated disease states.
1. A peptide which is capable of
inhibiting kinase activity of Janus kinase (JAK), the peptide consisting of the amino acid sequence:
X1-X2-X3-X4-X5-X6-X7-X8
(SEQ ID NO: 52)
wherein:
X1 is proline or glycine;
X2 is alanine, valine, leucine or isoleucine;
X3 is glutamate or aspartate;
X4 is phenylalanine or tyrosine;
X5 is leucine or methionine or isoleucine;
X6 is arginine or lysine;
X7 is methionine or leucine or isoleucine; and
X8 is isoleucine or leucine or methionine.
2. The peptide of claim 1 wherein X1 is proline, X2 is alanine, X3 is glutamate, X4 is phenylalanine, X5 is methionine, X6 is arginine, X7 is methionine and X8 is isoleucine.
3. The peptide of claim 1 wherein X4 is phenylalanine.
4. The peptide of claim 1 wherein X7 is methionine.
5. The peptide of claim 1 wherein X8 is isoleucine.
6. The peptide of claim 1 wherein the peptide is cyclic.