Thioctic acid modification of oligonucleotides using an H-phosphonate

The H-phosphonate of a derivative of thioctic acid (TA) was synthesised and used to introduce a disulfide moiety at the 5′-end of oligonucleotides. This method overcomes the difficulties experienced with the phosphoramidite approach when employing a cyclic disulfide in the starting alcohol. The disulfide-modified oligonucleotides are subsequently used in metallic nanoparticle (Au and Ag) and surface functionalisation for sensitive, sequence specific analytical detection strategies.

A convenient route for 5′-modification of an oligonucleotide with a cyclic disulfide, thioctic acid, is reported using the H-phosphonate method.