Site-Specific DNA Post-Synthetic Modification via Fast Photocatalytic Allylation

Abstract

Developing new chemical toolboxes for site-specific nucleic acid post-synthetic modification is of great challenge and urgently required for precisely expanding DNA functionality, which holds significant research implications in nucleic acid chemistry, biology, and beyond. Herein, we demonstrate the first site-specific DNA post-synthetic modification via fast photocatalytic allylation under visible light. Allyl sulfone groups were introduced into oligonucleotides, not only at the terminal sites via traditional amidation reactions but also at the internal and terminal sites via DNA solid-phase synthesis. This visible-light-induced photocatalytic decarboxylative allylation proceeds rapidly on the oligonucleotides bearing allyl sulfone groups under open-to-air conditions within minutes, exhibiting excellent chemoselectivity and compatibility with various functional groups while retaining the DNA integrity. Specifically, introducing allyl sulfone into oligonucleotides via DNA solid-phase synthesis enables site-specific DNA modification on chemically synthesized single-stranded DNA at internal and terminal positions, hybridized double-stranded DNA, and enzymatically amplified long-chain DNA under visible light. The versatile reactivity of allyl sulfone scaffolds further enables diverse on-DNA photocatalytic transformations, promising to advance chemical toolboxes for DNA post-synthetic modification through diverse photochemical methods.