Liu Yuan, Hou Weijia, Sun Hao, Cui Cheng, Zhang Liqin, Jiang Ying, Wu Yongxiang, Wang Yanyue, Li Juan, Sumerlin Brent S, Liu Qiaoling, Tan Weihong
Molecular Science and Biomedicine Laboratory , State Key Laboratory of Chemo/Bio-Sensing and Chemometrics , College of Life Sciences , College of Chemistry and Chemical Engineering , Aptamer Engineering Center of Hunan Province , Hunan University , Changsha , Hunan 410082 , China . Email:
Center for Research at Bio/Nano Interface , Department of Chemistry , Department of Physiology and Functional Genomics , Health Cancer Center , UF Genetics Institute , McKnight Brain Institute , University of Florida , Gainesville , Florida 32611-7200 , USA . Email:
Chem Sci. 2017 Sep 1;8(9):6182-6187. doi: 10.1039/c7sc01447c. Epub 2017 Jun 22.
Bioconjugation based on crosslinking primary amines to carboxylic acid groups has found broad applications in protein modification, drug development, and nanomaterial functionalization. However, proteins, which are made up of amino acids, typically give nonselective bioconjugation when using primary amine-based crosslinking. In order to control protein orientation and activity after conjugation, selective bioconjugation is desirable. We herein report an efficient and cysteine-selective thiol-ene click reaction-based bioconjugation strategy using colloidal nanoparticles. The resulting thiol-ene based aptamer and enzyme nanoconjugates demonstrated excellent target binding ability and enzymatic activity, respectively. Thus, thiol-ene click chemistry can provide a stable and robust crosslinker in a biocompatible manner for bioconjugation of any thiol-containing biomolecule with nanomaterials. This will open more opportunities for applications of thiol-ene reactions and functional colloidal nanoparticles in chemical biology.
基于将伯胺交联到羧酸基团的生物共轭在蛋白质修饰、药物开发和纳米材料功能化方面有着广泛的应用。然而，由氨基酸组成的蛋白质在使用基于伯胺的交联时通常会产生非选择性生物共轭。为了在共轭后控制蛋白质的方向和活性，选择性生物共轭是很有必要的。我们在此报告一种基于高效且对半胱氨酸具有选择性的硫醇-烯点击反应的生物共轭策略，该策略使用了胶体纳米颗粒。所得到的基于硫醇-烯的适配体和酶纳米共轭物分别表现出优异的靶标结合能力和酶活性。因此，硫醇-烯点击化学能够以生物相容的方式为任何含硫醇的生物分子与纳米材料的生物共轭提供一种稳定且坚固的交联剂。这将为硫醇-烯反应和功能性胶体纳米颗粒在化学生物学中的应用开辟更多机会。
