The present invention defines an assay useful for screening libraries of synthetic or biological compounds for their ability to bind specific DNA test sequences. The assay is also useful for determining the sequence specificity and relative DNA-binding affinity of DNA-binding molecules for any particular DNA sequence. Also described herein are potential applications of the assay, including: 1) the detection of lead compounds or new drugs via the mass screening of libraries of synthetic or biological compounds (i.e., fermentation broths); 2) the design of sequence-specific DNA-binding drugs comprised of homo- or hetero-meric subunits of molecules for which the sequence specificity was determined using the assay; and 3) the use of molecules for which sequence specificity was determined using the assay as covalently attached moieties to aid in the binding of nucleic acid or other macromolecular polymers to nucleic acid sequences.