Peptides and peptidomimetics having anti-proliferative activity and/or that augment nucleic acid damaging agents or treatments

DETAILED DESCRIPTION The invention provides compounds including peptides and peptidomimetics that inhibit cell proliferation.
The invention compounds are therefore useful for treating cell proliferative disorders or physiological conditions characterized by undesirable or unwanted cell proliferation, such as benign and malignant tumor cells.
The ability of invention peptides and peptidomimetics to inhibit cell proliferation appears to be due at least in part to abrogation of the cell cycle G2 checkpoint.
Because cells can be induced to enter the cell cycle G2 checkpoint in response to nucleic acid damage to allow the cell to repair the damage before DNA replication and cell division occurs, by inhibiting the G2 checkpoint, invention peptides and peptidomimetics sensitize cells to nucleic acid damaging agents and treatment protocols.
Cells that accumulate enough nucleic acid damage will be unable to complete repair of the damaged nucleic acid because the G2 checkpoint is disrupted.
Such cells will exhibit decreased proliferation (e.
g.
, due to mutation of a gene critical for survival that is not repaired) and eventually undergo apoptosis.
Cells having a normal G1 are less susceptible to accumulating damaged nucleic acid since nucleic acid repair can also take place during G1.
Thus, normal cells are less susceptible to the effects of the invention compounds.
However, cells having an impaired or disrupted cell cycle G1 checkpoint are more likely to accumulate damaged nucleic acid because the G1 checkpoint is impaired or disrupted making it less likely that the cells can completely repair the damaged nucleic acid.
Thus, treating G1 impaired or disrupted cells with an invention peptide or peptidomimetic that disrupts the G2 checkpoint makes the cells even less likely to be able to complete repair of the damaged nucleic acid.
G1 impaired or disrupted cells are therefore particularly sensitive to such invention peptides and peptidomimetics.
Thus, invention compounds including peptides and peptidomimetics can be used to inhibit or prevent cell proliferation in general and in particular inhibit proliferation of cells having an impaired or disrupted GI checkpoint