The ability of steroids to regulate transcription from specific genes has been well established. We have examined the mechanism of DNA binding by individually synthesizing the putative """"""""zinc finger peptides"""""""" from the rat glucocorticoid receptor. Circular Dichroism experiments demonstrated a significant alteration in secondary structure in the presence of zinc that is pH dependent and correlates directly with DNA binding. The results from DNA binding experiments establish that single zinc finger peptides can successfully compete with the intact DNA binding domain in a novel gel shift competition assay. Mutations in conserved cysteines fail to compete. Mutations in the CII finger establish that the final cysteine is required for DNA binding. Finally we have synthesized a unique biological reagent that converts the CII finger peptide into a specific endonucleolytic agent. The results suggest that a single synthetic """"""""finger peptide"""""""" is able to bind to DNA in a sequence specific manner.
