Tel Aviv University

Yeda Research and Develpment & Co. Ltd

Avital Licht-Murava

Hagit Eldar-Finkelman

Miriam Eisenstein

Batya Plotkin

Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are converted to inhibitors of GSK-3 upon interacting with the enzyme's catalytic site and hence act as disease-selective inhibitors for treating conditions associated with increased activity and/or expression of GSK-3. Each of the disclosed peptides is independently of no more than 15 amino acid residues, and has an amino acid sequence which comprises a ZXXXZ(p) recognition motif of GSK-3, wherein Z(p) is a phosphorylated serine or threonine residue; Z is a phosphorylatable serine or threonine residue, and each of X, Xand Xis independently any amino acid, as defined in the specification. Further disclosed are methods of identifying a putative substrate-competitive peptide inhibitor of GSK-3 which are effected by computational modeling and screening.

Glycogen synthase kinase-3 inhibitors

Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3. Also disclosed are GSK-3 substrate competitive inhibitors which bind to the defined binding site subunit in the enzyme. Also disclosed are mutants of GSK-3 and uses thereof for identifying a putative GSK-3 substrate competitive inhibitor.

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Tel Aviv, Israel

Avital Licht-Murava