Ligand-promoted dimerization of oligonucleotides binding cooperatively to DNA

Abstract

In biological systems, specific protein-DNA interactions are often modulated by ligands as in the regulation of gene expression. Many transcription factors arc active as dimers, but inactive as monomes. In at least one case, dimerization is regulated by an additional protein cofactor. We recently described the design of a triple helical complex compnsmg two oligonucleotides which bind adjacent sites on DNA cooperatively through dimerization. If dimerizat1on could be controlled by additional ligands such an artificial nucleic acid system would be analogous to the naturally occurring inducible protein systems. We now report that the stability of the dimerization domain can be enhanced by a small molecule, echinomycin (E). The strengths of ligand-promoted control of oligonucleotides binding cooperatively to DNA are quantitated by affinity cleaving.

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