Max-Planck-Institute for Polymer Research , Ackermannweg 10, 55128 Mainz, Germany.
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University , Chengdu 610031, P.R. China.
Bioconjug Chem. 2018 Jan 17;29(1):29-34. doi: 10.1021/acs.bioconjchem.7b00675. Epub 2017 Dec 20.
The attachment of two different functionalities in a site-selective fashion represents a great challenge in protein chemistry. We report site specific dual functionalizations of peptides and proteins capitalizing on reactivity differences of cysteines in their free (thiol) and protected, oxidized (disulfide) forms. The dual functionalization of interleukin 2 and EYFP proceeded with no loss of bioactivity in a stepwise fashion applying maleimide and disulfide rebridging allyl-sulfone groups. In order to ensure broader applicability of the functionalization strategy, a novel, short peptide sequence that introduces a disulfide bridge was designed and site-selective dual labeling in the presence of biogenic groups was successfully demonstrated.
在定点方式下将两种不同的功能附接在一个位置上，这对蛋白质化学来说是一个巨大的挑战。我们报告了利用半胱氨酸在其游离（巯基）和保护的氧化（二硫键）形式下的反应性差异，实现对肽和蛋白质的定点双官能化。白细胞介素 2 和 EYFP 的双官能化以逐步方式进行，应用马来酰亚胺和二硫键重新桥接烯丙基-砜基基团，没有生物活性的损失。为了确保该官能化策略的更广泛适用性，设计了一种新颖的短肽序列，该序列引入了二硫键，并成功地在存在生物源基团的情况下实现了定点双标记。
