RNA-peptide conjugate synthesis by inverse-electron demand Diels-Alder reaction.

Here we report an efficient method for the synthesis of RNA-peptide conjugates by inverse-electron demand Diels-Alder reaction. Various dienophiles were enzymatically incorporated into RNA and reacted with a chemically synthesized diene-modified peptide. The Diels-Alder reaction proceeds with near-quantitative yields in aqueous solution with stoichiometric amounts of reactants, even at low micromolar concentrations.