Down-regulation of H tau 40 protein expression by minor groove binders.

The DNA minor groove binders SN6999, SN6570, and SN6113, structurally related to netropsin and distamycin, were investigated for sequence-specific interactions with the 154 base pair cDNA fragment of the human tau 40 protein, involved in pathology of Alzheimer's disease. Footprinting results indicated that both the former compounds displayed a pronounced AT-preference, while the latter SN-derivative bound to DNA in a non-sequence specific manner. The influence of these ligands on the protein synthesis was analysed using monoclonal antibodies against h tau protein. Both sequence specific binders markedly impeded protein synthesis. The non-specific binder, however, did not affect protein biosynthesis.