Pharmacological agents active at the level of gene transcription are identified in high throughput drug screening assays. The methodsinvolve combining a labeled transcription factor, a nucleic acid coupled to a ligand, a candidate pharmacological agent and a receptorimmobilized on a solid substrate, such as a microtiter plate, filter, or bead. The nucleic acid has at least that portion of a nucleotidesequence naturally involved in the regulation of the transcription of the gene which is necessary for sequence-specific interaction with thetranscription factor. The resultant combination is incubated under conditions whereby the receptor is bound to the ligand and, but for thepresence of said candidate pharmacological agent, the transcription factor is sequence-specifically bound to the nucleic acid. Unboundtranscription factor is then removed or washed from the solid substrate and labelled, sequence-specifically bound transcription factor isdetected. Incubates which include candidate agents which alter transcription factor binding deviate from control incubates in terms oflabel signal - typically, binding is disrupted and the signal is diminished. In a preferred embodiment, the entire process is performed by acomputer-controllable electromechanical robot with an axial rotatable arm.
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