Bromopyridazinedione-mediated protein and peptide bioconjugation

Abstract

Bromopyridazinedione-mediated bioconjugation to a cysteine containing protein and a disulfide containing peptide is reported. These bioconjugates exhibit excellent hydrolytic stability and cleave in an aqueous, thiol-mediated reducing environment.

A mild TCEP-based para-azidobenzyl cleavage strategy to transform reversible cysteine thiol labelling reagents into irreversible conjugates

“…16 Recently, we have described a novel, reversible approach to cysteine bioconjugation through the use of bromomaleimides and bromopyridazinediones. 17 To date, our approach has provided 50 access to complex bioconjugates in high yields, without prior activation of reagents with reliable, reversible conjugation.…”

Reversible protein affinity-labelling using bromomaleimide-based reagents

“…5 To date, our approach has provided access to complex bioconjugates in high yields, without prior activation of reagents. As part of this programme, we reported a new bromomaleimide-based affinity-tagging reagent which allows for the facile and reversible biotinylation of proteins.…”

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

“…Dibromopyridazinediones (Figure A, V) were reported by Caddick and Chudasama for targeting disulfide bridges in peptides, Fab and antibodies . The synthesis of dibromopyridazinediones can be achieved over three steps by the initial condensation of maleic anhydride with disubstituted hydrazine followed by sequential dibromination/elimination steps with a moderate overall yield (≈60 %) .…”