Glycogen synthase kinase-3 inhibitors

Abstract

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.