Synthesis of oligonucleotides containing 2-N-heteroarylguanine residues and their effect on duplex/triplex stability

To systematically understand the effect of 2-N-heteroarylguanine (G HA ) modification on the stability of higher-order DNA structures, nucleoside derivatives and oligodeoxyribonucleotides containing guanine residues modified with four kinds of hereroaryl groups on the 2-amino group were synthesized. The stabilities of the DNA duplex and the parallel-oriented DNA triplex containing these G HA s were studied by measuring their melting temperatures ( T m ). T m experiments and DFT calculations of the modified guanine nucleobases suggested that the base pair formation energy and stability of the two conformations, i.e. , the open- and closed-type conformations, are key to determining the stability of the DNA duplex. Finally, the DNA triplex was destabilized when modified guanine residues were introduced into triplex-forming oligonucleotides. Pyridine, pyrimidine, and pyrazine residues were introduced to the amino group of deoxyguanosine to modulate the base pairing properties.