Fast thiol–maleamic methyl ester addition for facile covalent cross-linking of oligonucleotides

Thiol-Michael-cross-linked oligodeoxynucleotides were synthesized through the thiol–maleamic acid methyl ester addition reaction. As a metal-free ‘click’ reaction, the cross-linked method was fast responsive and highly sensitive. The newly synthesized oligodeoxynucleotides were thermally stable and their global structures retained those of non-cross-linked oligodeoxynucleotides and showed responsive reaction to different DNA restriction enzymes.