Technical & Educational Articles

Chemical modification of oligodeoxynucleotides (ODNs) has been receiving increasing attention in the fields of gene therapeutics and genetic diagnosis.[1,2] One promising approach is an internucleoside linkage modification of the ODNs. An N3’!P5’-phosphoramidate-linked ODN, in which the 3’-oxygen atom is replaced with a nitrogen atom, forms a stable duplex structure with its DNA or RNA complement.[3] On the other hand, P3’!N5’-phosphoramidate-linked ODNs (5’-amino-DNA, Scheme 1a), with a 5’-nitrogen atom instead of an oxygen atom, can be hydrolyzed at the phosphoramidate linkage under mild acidic conditions.[4] This property of 5’-amino-DNA has attracted much attention and has been applied to a DNA-sequence determination.[5, 6] However, the 5’-amino-DNA modification of ODNs decreases the hybridizing ability with its complementary strand.[7,8] This disadvantage of 5’-amino-DNA may be caused by an inappropriate g dihedral angle (N5’–C5’–C4’–C3’). 1H NMR analysis of a 5’- amino-DNA dimer revealed that the orientation of the C4’– C5’ bond is predominantly +ap (g
1808) or sc (g
608), which is different from that in a typical DNA/DNA or RNA/ RNA duplex (+sc, g
608).