In this synthetic procedure, a seven-step protocol for the preparation of monosubstituted 3-bromo-1,2,4,5-tetrazine is presented. The procedure features efficient transformations and purification methods starting from commercially readily available materials affords title compound on gram scale with 13 % overall yield in reliable purity (>97 %). Detailed experimental procedures, supported by im...

Significance The manipulation of proteins in a site-selective manner underpins much modern protein chemistry. A careful evaluation selenomethionine benzylation led to the identification highly efficient bromobenzyl linker for bioconjugation. This selenonium-forming ligation reaction can efficiently link other complex molecules such as synthetic peptides, polymers, or reactive handles. selenoniu...

Protein bioconjugation frequently makes use of aldehydes as reactive handles, with methods for their installation being highly valued. Here a new, powerful strategy to unmask a reactive protein aldehyde is presented. A genetically encoded caged glyoxyl aldehyde, situated in solvent-accessible locations, can be rapidly decaged through treatment with just one equivalent of allylpalladium(ii) chlo...

Herein we report an umpolung strategy for the bioconjugation of selenocysteine in unprotected peptides. This mild and operationally simple approach takes advantage of the electrophilic character of an oxidized selenocysteine (Se-S bond) to react with a nucleophilic arylboronic acid to provide the arylated selenocysteine within hours. This reaction is amenable to a wide range of boronic acids wi...

Advances in bioconjugation and native protein modification are appearing at a blistering pace, making it increasingly time consuming for practitioners to identify the best chemical method for modifying a specific amino acid residue in a complex setting. The purpose of this perspective is to provide an informative, graphically rich manual highlighting significant advances in the field over the p...