Naonori Inoue

Oligodeoxynucleotides Containing 3‐Bromo‐3‐deazaadenine and 7‐Bromo‐7‐deazaadenine 2′‐Deoxynucleosides as Chemical Probes to Investigate DNA–Protein Interactions

We describe the design and proof of concept of a pair of chemical probes for investigating DNA–protein interactions—specifically, the incorporation of 7‐bromo‐7‐deazaadenine and 3‐bromo‐3‐deazaadenine 2′‐deoxynucleosides (Br7C7dA and Br3C3dA) into oligodeoxynucleotides (ODNs)—and their utility. Whereas the bromo substituent of the Br7C7dA unit in an ODN duplex acts sterically to inhibit binding with NF‐κB, which interacts with the duplex in its major groove, the bromo substituent of the Br3C3dA unit acts sterically to inhibit binding with RNase H, which interacts with the duplex in its minor groove. In addition, the utilization of ODNs containing 7‐deazaadenine and 3‐deazaadenine 2′‐deoxynucleosides (C7dA and C3dA), together with the pair of chemical probes, afforded valuable information on the requirement for nitrogen atoms located in either the major or minor grooves. Accordingly, we were able to show the utility of ODNs containing Br7C7dA, Br3C3dA, C7dA, and C3dA for the investigation of DNA–protein interactions.