Protein Conjugation by Electrophilic Alkynylation Using 5-(Alkynyl)dibenzothiophenium Triflates,Bioconjugate Chemistry

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Protein Conjugation by Electrophilic Alkynylation Using 5-(Alkynyl)dibenzothiophenium Triflates
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-07-07 , DOI: 10.1021/acs.bioconjchem.1c00317
Victor Laserna ₁ , Alena Istrate ₁ , Kevin Kafuta ₂ , Tuuli A Hakala ₁ , Tuomas P J Knowles _{1,

3} , Manuel Alcarazo ₂ , Gonçalo J L Bernardes _{1,

4}

Affiliation

5-(Alkynyl)dibenzothiophenium triflates are introduced as new reagents to prepare different protein conjugates through site-selective cysteine alkynylation. The protocol developed allows a highly efficient label of free cysteine-containing proteins with relevant biological roles, such as ubiquitin, the C2A domain of Synaptotagmin-I, or HER2 targeting nanobodies. An electrophilic bis-alkynylating reagent was also designed. The second alkynylating handle thus introduced in the desired protein enables access to protein–thiol, protein–peptide, and protein–protein conjugates, and even diubiquitin dimers can be prepared through this approach. The low excess of reagent needed, mild reaction conditions used, short reaction times, and stability of the S–C(alkyne) bonds at physiological conditions make this approach an interesting addition to the toolbox of classical, site-selective cysteine-conjugation methods.

中文翻译：

使用 5-（炔基）二苯并噻吩三氟甲磺酸盐通过亲电炔基化进行蛋白质缀合

5-（炔基）二苯并噻吩三氟甲磺酸盐作为新试剂被引入，以通过位点选择性半胱氨酸炔基化制备不同的蛋白质缀合物。开发的协议允许对具有相关生物学作用的游离半胱氨酸蛋白进行高效标记，例如泛素、Synaptotagmin-I 的 C2A 域或 HER2 靶向纳米抗体。还设计了亲电双炔化试剂。因此在所需蛋白质中引入的第二个炔基化处理能够获得蛋白质 - 硫醇、蛋白质 - 肽和蛋白质 - 蛋白质缀合物，甚至可以通过这种方法制备双泛素二聚体。所需试剂用量少，反应条件温和，反应时间短，

更新日期：2021-08-19

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