The compositions and methods disclosed herein provide heterobifunctional
programmable genotoxic compounds that can be designed to kill selected
cells present in a heterogenous cell population. The present compounds
comprise a first agent that inflicts damage on cellular DNA, and a second
agent that attracts a macromolecular cell component such as a protein,
which in turn shields genomic lesions from repair. Unrepaired lesions
therefore persist in the cellular genome and contribute to the death of
selected cells. In contrast, lesions formed in nonselected cells, which
lack the cell component, are unshielded and thus are repaired. As a
result, compounds described herein are less toxic to nonselected cells.
Compounds of this invention can be designed to cause the selective
killing of transformed cells, viral-infected cells and the like.