Sequence-directed DNA-binding molecules compositions and methods
The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule.
1. A method for altering the binding characteristics of a DNA-binding protein to a duplex DNA, comprising
contacting the duplex DNA with a small molecule characterized by sequence-preferential binding to a target region where, when the small molecule is bound to the target region, the small molecule is adjacent to a binding site for the DNA-binding protein, at a concentration of small molecule effective to alter the binding of the DNA-binding protein to its binding site of the duplex DNA.