Metal-Dependent Base Pair Switching of N,N-Dicarboxymethyl-5-Aminouracil Nucleosides

Abstract

The base pair switching of U^OH has had limited application because it requires the consecutive introduction of multiple U^OH bases into DNA strands. In this chapter, I aimed to develop metal-responsive base pair switching by a singly incorporated ligand-type nucleobase. To this end, I designed N,N-dicarboxymethyl-5-aminouracil (dcaU) containing an iminodiacetate ligand. The dcaU base was expected to show higher coordination ability than U^OH due to its negative charges and chelate effects. After obtaining dcaU phosphoramidite, dcaU-containing DNA strands were synthesized by an automated DNA synthesizer. In the presence of Gd^III ions, a DNA duplex with a dcaU–dcaU pair was significantly stabilized due to the formation of dcaU–Gd^III–dcaU pairs. As a result, the addition of Gd^III ions reversed the relative stability of two duplexes containing dcaU–A or dcaU–dcaU pairs, indicating base pair switching between dcaU–A and dcaU–Gd^III–dcaU. The base pair switching of dcaU was further applicable for Gd^III-responsive DNA strand exchange. These results showed that the efficiency of the base pair switching can be rationally controlled by careful design of ligand-type nucleobases.