Synthesis of peptide- and drug-oligonucleotide conjugates via a photocatalyzed decarboxylative Giese reaction.

Herein, we report a photocatalyzed decarboxylative Giese reaction for the late-stage functionalization of 5'-COOH oligonucleotides. Under mild visible-light conditions, C4' radicals are generated and trapped by diverse Michael acceptors, including simple alkenes, Dha-containing peptides, and alkene-bearing drug molecules. This method enables the rapid synthesis of peptide- and drug-oligonucleotide conjugates and is applicable to dinucleotides as well as 3-4 nt oligonucleotides on a microscale (10-100 nmol).