Synthesis of Adenosine Diphosphate Ribose Histidine

Adenosine diphosphate ribosylated histidine (His-ADPr) is a vital signaling molecule for the bacterial immune system, the antiphage system in particular. In this unique second messenger molecule, the distal nitrogen of the histidine side chain is ribosylated in a β fashion. Here, we describe the synthesis of this bacterial metabolite and its triazole isostere and evaluate the stability of His-ADPr to relevant ribosyl hydrolases.