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 °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.

以生物正交单元为特征并导致稳定加合物形成的连接方法是在生物学环境中应用的理想候选者。然而，大多数可用的策略依赖于需要小心处理的高反应性物质，或依赖于促反应性官能团的激活。我们在这里报告了一种依赖于稳定的 2,5-二酮的接近诱导连接反应，该反应可以在酸性条件下从 2,5-二烷基呋喃结构单元和肼亲核试剂中方便地生成。这种在生理条件下进行的生物正交连接不需要任何刺激或触发，并导致形成哒嗪加合物，该加合物在恶劣条件下（90°C 下 24 小时）表现出出色的稳定性。该反应应用于 PNA-PNA 加合物的形成，DNA 和 RNA 模板连接，以及在溶液中形成肽-肽加合物。这种方便的方法进一步在塑料和玻璃表面上实施，以实现可自我寻址的共价结构。