Orthogonal synthesis of a versatile building block for dual functionalization of targeting vectors

Abstract Dual functionalization of targeting vectors, such as peptides and antibodies, is still synthetically challenging despite the increasing demand for molecules serving multiple purposes (i.e., optical nuclear imaging). Our strategy was to synthesize a versatile building block via orthogonal incorporation chemical entities (e.g., radionuclide chelator, fluorescent dye, cytotoxic drugs, click handle, albumin binder) in order prepare various dual functionalized biovectors. The functional groups were introduced on using straightforward reactions. Thus, an azidolysine biogenic lysine installed into allow coupling second group regioselective conjugation biovector strain-promoted azide–alkyne cycloaddition, while first inserted during solid-phase peptide synthesis. To extend applicability large biomolecules, DBCO-maleimide linker clicked present maleimide that could react with exposed sulfhydryl cysteine residues. exemplify possibilities offered by block, we synthesized two dual-functionalized compounds containing 2,2′,2″′,2‴-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid chelator binder ( 4a ) blood half-life radiolabeled biovectors or handle 4b enable late-stage reaction; conjugated model cyclic bearing short thiolated at N -terminal position, single step thiol–maleimide Michael addition. Both peptides, 9a 9b , obtained rapidly high purity (>95%) labeled [ 111 In]InCl 3 . radiopeptides showed good stability mouse serum PBS buffer.