Design and synthesis of ortho-phthalaldehyde phosphoramidite for single-step, rapid, efficient and chemoselective coupling of DNA with proteins under physiological conditions

ortho-Phthalaldehyde (OPA) phosphoramidite with high reaction activity was designed and synthesized for labelling oligodeoxynucleotides (DNA). The DNA modified with OPA (OPA-DNA) can covalently couple with native proteins rapidly and efficiently via a condensation reaction with the formation of phthalimidines, which provides a highly efficient method for bioconjugation of DNA and native proteins under physiological conditions.