Synthesis of Hetero-bifunctional Azobenzene Glycoconjugates for Bioorthogonal Cross-Linking of Proteins

Modification of proteins with azobenzene derivatives allows their form and function to be controlled by photochemical E/Z isomerization of the azobenzene N=N bond. Because azobenzene glycoconjugates (ABGs) are particularly promising cross-linkers for the modification of peptides and proteins, we advanced the collection of so far known homo-bifunctional ABGs with the synthesis of hitherto unknown hetero-bifunctionalized ABGs. Alkyne and alkene, alkyne and sulfhydryl, and azido and alkene functions were combined in one molecule to serve as bioorthogonal reaction pairs. With this, access to a multitude of photosensitive proteins is provided.