Antibody dual-functionalisation enabled through a modular divinylpyrimidine disulfide rebridging strategy

Herein we report the development of a methodology for the dual-functionalisation of IgG antibodies. This is accomplished through the combination of disulfide rebridging divinylpyrimidine technology, with bicyclononyne and methylcyclopropene handles to facilitate sequential SPAAC and IEDDA reactions. Advantageously, the strategy does not require metal catalysis and avoids the need for purification between functionalisation steps. A modular and metal-free chemical methodology for the synthesis of dual-functionalised antibody-drug conjugates.