Double Duty For DNA-Binding Molecules

A new class of DNA-binding molecules that can accomplish sequence-specific binding and fluorescent reporting within one molecular platform has been created by David M. Chenoweth, Anne Viger, and Peter B. Dervan of California Institute of Technology (J. Am. Chem. Soc., DOI: 10.1021/ja0682576). These oligomers "announce" their association with double-stranded DNA by means of a fluorescent moiety incorporated within the binding module. Previously, when researchers wanted to locate and visualize a specific DNA sequence, they had two options: make a DNA-binding molecule tagged to a separate bulky fluorescent reporter, or use a DNA-binding molecule that requires harsh denaturation conditions in order to hybridize to DNA. The new compounds modify Dervan's well-established DNA-binding polyamides to introduce a series of heterocyclic rings that provide the fluorescent kick. The oligomers can be applied as "chromosome paints" to identify desired DNA sequences, Chenoweth says. So far, the fluorescent tags bind best to sections of DNA containing guanine (G), such as TACG or GGGG sequences, but an expansion of the target base-pair lexicon is in the works.