A variety of electronic DNA array devices and techniques have been developed that allow electric field enhanced hybridization to be carried out under special low-conductance conditions. These devices include both planar microelectronic DNA array/chip devices as well as electronic microtiter plate-like devices. Such "active" electronic devices are able to provide controlled electric (electrophoretic) fields that serve as a driving force to move and concentrate nucleic acid molecules (DNA/RNA) to selected microlocation test-sites on the device. In addition to ionic strength, pH, temperature and other agents, the electric field provides another controllable parameter that can affect and enhance DNA hybridization. With regard to the planar microelectronic array devices, special low-conductance buffers were developed in order to maintain rapid transport of DNA molecules and to facilitate hybridization within the constrained low current and voltage ranges for this type of device. With regard to electronic microtiter plate type devices (which do not have the low current/voltage constraints), the use of mixed buffers (low conductance upper chamber/high conductance lower chamber) can be used in a unique fashion to create favorable hybridization conditions in a microzone within the test site location. Both types of devices allow DNA molecules to be rapidly and selectively hybridized at the array test sites under conditions where the DNA in the bulk solution can remain substantially denatured.

A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC(50) = 10 &mgr;M and aromatic derivative 35 has IC(50) = 2 &mgr;M for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.

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