Journal
COMMUNICATIONS CHEMISTRY
Volume 4, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42004-021-00584-1
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Funding
- FWO
- European Union [665501, 721613]
- UGent Industrieel OnderzoeksFonds [F2019/IOF-ConcepTT/188, F2020/IOF-ConcepTT/111]
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A new method has been developed for proximity-induced ligation reactions in a biological context, resulting in stable products. This method does not require the activation of highly reactive species or pre-reactive functional groups, showcasing excellent stability and convenience.
Proximity-based ligations commonly require an external stimulus such as a catalyst or irradiation, or highly reactive functional groups. Here the reaction of alpha effect nucleophiles and 2,5-dioxopentanyl derivatives allows direct proximity-based ligation while avoiding highly reactive moieties. Ligation methodologies featuring bio-orthogonal units and leading to the formation of a stable adduct are the ideal candidates for being applied in a biological context. However, most of the available strategies rely on highly reactive species that require careful handling, or on the activation of pro-reactive functional groups. We here report on a proximity-induced ligation reaction that relies on a stable 2,5-dione, that can be conveniently generated under acidic conditions from a 2,5-dialkylfuran building block, and hydrazine nucleophiles. This bio-orthogonal ligation, which proceeds under physiological conditions, does not require any stimulus or trigger and leads to the formation of a pyridazinium adduct that demonstrates excellent stability under harsh conditions (24 h at 90 degrees C). The reaction was applied to the formation of PNA-PNA adducts, DNA- and RNA-templated ligations, and for the formation of peptide-peptide adducts in solution. This convenient methodology was further implemented on plastic and glass surfaces to realize self-addressable covalent constructs.
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