Abstract: The present invention is based on the surprising and unexpected discovery of new and useful polyamide-alkylator conjugates. As a result of their DNA binding properties, polyamides deliver reactive moieties for covalent reaction at specific DNA sequences and thereby inhibit DNA-protein interactions. Thus, site specific alkylation of DNA is a useful tool to regulate gene expression. In addition to competing with transcription factors or promoters, the conjugates of the present invention will be used to target a gene's coding region. This will allow using synthetic chemistry to create a new class of gene specific “knockout” reagents which will be useful in biological disciplines.