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Updated: Mar 28, 2026

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
Vitamin B12 Suitably Tailored for Disulfide-Based Conjugation
Aleksandra Wierzba1, Monika Wojciechowska2, Joanna Trylska2
1Institute of Organic Chemistry, Polish Academy of Sciences , M. Kasprzaka 44/52, 01-224 Warsaw, Poland.
Abstract:
Vitamin B12 has been proposed to be a natural vector for the in vivo delivery of biologically active compounds. Most synthetic methodologies leading to vitamin B12 conjugates involve functionalization at the 5' position via either carbamate-based linkages or using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), resulting in stable conjugates that are not cleaved within the cell. We have developed a novel vitamin B12 derivative suitably tailored for disulfide-based conjugation that can undergo cleavage in the presence of glutathione, the most abundant thiol in mammalian cells. This active compound is simple to prepare and allows for the direct disulfide-based attachment of therapeutic cargos.
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