Patent ID: 6420118
Filing Date: 2002-07-16
Classification: A61K,A61P,C07K

Abstract:
A method for identifying p53 mutants whose ability to bind DNA may be activated by peptides or peptidomimetics corresponding to all or a portion of the negative regulatory region which maps to residues 361-383 of p53, comprising mixing a sample containing a p53 mutant protein with a peptide or a peptidomimetic which competes with an endogenous p53 negative regulatory region for binding with a negative regulatory region of p53, said peptide or said peptidomimetic containing at least four sequential amino acids from a negative regulatory region which maps to residues 361-383 of p53 (SEQ ID NO. 2), said peptide not being a subfragment of human p53, wherein said peptide or said peptidomimetic activates, in a p53 DNA binding assay, DNA binding of wild-type p53 or a p53 mutant containing a single amino acid substitution, said mutant selected from the group consisting of p53-ser239, p53-his273, p53-gln248, p53-trp282, and p53-cys273, and said peptide or said peptidomimetic containing residues 363-373 (SEQ ID NO. 4), 368-380 (SEQ ID NO. 5), 373-383 (SEQ ID NO. 6), 371-383 (SEQ ID NO. 7), 363-382 (SEQ ID NO. 8), 367-386 (SEQ ID NO.9), 363-386 (SEQ ID NO 10), 362-386 (SEQ ID NO. 11), 360-386 (SEQ ID NO. 12), 363-370 (SEQ ID NO. 14), 368-373 (SEQ ID NO. 15), 368-372 (SEQ ID NO. 16), 369-373 (SEQ ID NO.17), 370-375 (SEQ ID NO. 18), or 370-374 (SEQ ID NO. 19) of human p53,and subjecting the mixed sample to a DNA binding assay which measures DNA binding of p53 or mutants thereof, wherein DNA binding of said p53 mutants is activated by said peptide or said peptidomimetic relative to DNA binding in the absence of said peptide or said peptidomimetic.