Methods of using therapeutic p53 peptides
AssigneeUniversity of the Sciences of Philadelphia
InventorsZhiyu Li, Michelle Parker
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Abstract
The present invention relates to compositions useful in inhibiting Bcl-XL or MCL-1 and disrupting p53-MDM2 and p53-MDMX interactions, and methods of using those compositions for treating a subject for conditions responsive to increasing p53 mediated activity or promoting p53 independent apoptosis, such as treating cancer. In some aspects, the compositions of this invention relate to fusion polypeptides comprising a human serum polypeptide and a p53-peptide, which can be, in some aspects, a p53 derived peptide and/or a p53 activating peptide.
Claims30
A method of disrupting BCL-XL and MCL-1 inhibition of apoptosis in a cell, the method comprising:
- (a) providing a fusion polypeptide;
- and
- (b) contacting the cell with the fusion polypeptide, thereby disrupting BCL-XL and MCL-1 inhibition of apoptosis in the cell,
- wherein the fusion polypeptide comprises a human serum albumin and a p53-peptide which comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:7, further comprising one or more anticancer agent, wherein the one or more anticancer agent is bound to the human serum albumin via covalent interactions, or is chemically conjugated to a natural ligand of the human serum albumin, wherein the natural ligand is bound to the human serum albumin.
A method of treating a subject with a cancer responsive to p53 inhibition of BCL-XL and MCL-1, and disrupting p-53 MDM2 interactions, the method comprising:
- (a) administering a therapeutically effective amount of a fusion polypeptide,
- wherein the fusion polypeptide comprises a serum albumin, or a fragment thereof, and a p53-peptide which comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:7,
- wherein the fragment retains the cell transport property, ligand binding property or both cell transport and ligand binding properties,
- wherein the fusion polypeptide comprises one or more anticancer agent, wherein the one or more anticancer agent is bound to the human serum albumin via covalent interactions, or is chemically conjugated to a natural ligand of the human serum albumin, wherein the natural ligand is bound to the human serum albumin.
A method of inducing apoptosis in a cell by one or more of:
- inhibiting BCL and MCL-1, disrupting p53-MDM2 interaction and disrupting p53-MDMX interaction, the method comprising:
- (a) providing a fusion polypeptide;
- and
- (b) contacting the cell with the fusion polypeptide, thereby inducing apoptosis in the cell,
- wherein the fusion polypeptide comprises a serum albumin, or a fragment thereof, and a p53-peptide which comprises SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:7,
- wherein the fragment retains cell transport property, ligand binding property or both cell transport and ligand binding properties, further comprising one or more anticancer agent, wherein the one or more anticancer agent is bound to the serum albumin via covalent interactions, or is chemically conjugated to a natural ligand of the serum albumin, wherein the natural ligand is bound to the serum albumin.
Dependencies are inferred from the claim text.