Regulation of Cl- channels by multifunctional CaM kinase.

cAMP kinase has been shown to mediate the cAMP pathway for regulation of Cl- channels in lymphocytes, but the mediator of an alternative, Ca2+ pathway has not been identified. We show here that Ca2+ ionophore activates Cl- currents in cell-attached and whole-cell patch-clamp recordings of Jurkat T lymphocytes, but this activation is not direct. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Furthermore, Cl- channels are activated in excised patches by purified CaM kinase in a fashion that mimics the effect of Ca2+ ionophore in cell-attached recordings. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation.     

Bifunctional 2-naphthyl propargylic sulfones exhibiting high DNA intercalating and alkylating activity.

A number of novel 2-naphthyl propargylic sulfones were synthesized as nucleic base alkylating agents. Extremely high DNA cleavage activity was observed for the sulfones with a free omega-hydroxyl group in the carbon chain in contrast to the ester conjugates possessing an additional intercalating unit.