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 protein rapidly and efficiently via condensation reaction with the formation of phthalimidines, which provides a highly efficient method for bioconjugation of DNA and native proteins under physiological conditions.