BH3 peptides and method of use thereof
OwnerStanley J. Korsmeyer, Anthony Letaiinventors
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Abstract
The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.
Claims32
An isolated peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:
- 1, 2 or 10.
An isolated peptide comprising the amino acid sequence selected from the group consisting of SEQ ID NOs:
- 3-7 or 11.
An isolated peptide of any one of SEQ ID NOs:
- 1-11.
A chimeric peptide comprising a first domain and a second domain wherein said first domain comprises the amino acid sequence selected from the group consisting of and SEQ ID NOs:
- 1-11 and said second domain comprising a translocation sequence which facilitates transport across a biological membrane.
A method of inducing apoptosis in a cell comprising contacting said cell with a composition comprising any if of SEQ ID NOs 1, 2 or 10 in an amount sufficient to induce apoptosis in said cell.
A method of sensitizing a cell to apoptosis comprising contacting said cell with a composition comprising any if of SEQ ID NOs:2-7 or 11 in an amount sufficient to sensitize said cell to apoptosis.
A method of screening for an apoptotic sensitizer compound comprising:
- (a) contacting mitochondria overexpressing an anti-apoptotic protein with a BID-like BH3 peptide to form a protein-peptide complex;
- (b) contacting said complex with a test compound;
- and
- (c) determining cytochrome c release from sad mitochondria, wherein an increase of cytochrome c release in the presence of said test compound compared to the absence of said compound indicates said compound is an apoptotic sensitizer compound
A transgenic non-human animal comprising a recombinant BCL-2 nucleic acid molecule stably integrated into the genome of said animal.
The animal of claim 22, wherein said further regulatory sequence is a promoter.
The animal of claim 27, wherein said rodent is a mouse.
A method for the production of a transgenic non-human animal, comprising introduction of a recombinant BCL-2 nucleic acid molecule into a germ cell, an embryonic cell, an egg cell or a cell derived therefrom.
Dependencies are inferred from the claim text.