Peng Qiang, Zang Berlin, Xiong Tao, Huang Chundong, Xu Ting, Zhang Chong, Ren Jun, Ji Fangling, Jia Lingyun
Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Bioengineering, Dalian University of Technology, Dalian, 116024, P. R. China.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, P. R. China.
Chem Commun (Camb). 2022 May 26;58(43):6316-6319. doi: 10.1039/d2cc01630c.
We here found that while Meldrum's acid as the reactive warhead allows for the attachment of a single chemical modification on aldehyde-containing proteins, pyrazolone derivatives in combination with a phosphine nucleophile enable protein dual site-specific conjugation with the same or distinct moieties. These reactions are efficient and convergent under biocompatible conditions and allow access to protein bioconjugates with superior stability, homogeneity and flexibility. Our work expands the repertoire of bioconjugation chemistries and offers opportunities to construct bioconjugates with defined structure that have potential for medical and biomaterial applications.
我们在此发现，虽然作为反应弹头的丙二酸可以使含醛蛋白质上附着单个化学修饰，但吡唑啉酮衍生物与膦亲核试剂结合能够实现蛋白质与相同或不同部分的双位点特异性共轭。这些反应在生物相容性条件下高效且具有收敛性，能够得到具有卓越稳定性、均一性和灵活性的蛋白质生物共轭物。我们的工作扩展了生物共轭化学的范围，并为构建具有明确结构、有医学和生物材料应用潜力的生物共轭物提供了机会。
