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Updated: Feb 6, 2026

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry
Published on: July 20, 2016
Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester
Takao Shoji1, Hiroki Fukutomi1, Yohei Okada2
1Department of Applied Biological Science, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan.
Abstract:
Artificial orthogonal bond formations such as the alkyne-azide cycloaddition have enabled selective bioconjugations under mild conditions, yet naturally occurring linkages between native functional groups would be more straightforward to elaborate bioconjugates. Herein, we describe the use of a phosphodiester bond as a versatile option to access various bioconjugates. An opposite activation strategy, involving 5'-phosphitylation of the supported oligonucleotides, has allowed several biomolecules that possess an unactivated alcohol to be directly conjugated. It should be noted that there is no need to pre-install artificial functional groups and undesired and unpredictable perturbations possibly caused by bioconjugation can be minimized.
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