Highly Stable and Selective Tetrazines for the Coordination-Assisted Bioorthogonal Ligation with Vinylboronic Acids.
Highly Stable and Selective Tetrazines for the Coordination-Assisted Bioorthogonal Ligation with Vinylboronic Acids.
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DOI：
10.1021/acs.bioconjchem.8b00439
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发表时间：
2018-09-19
影响因子：
4.7
通讯作者：
Bonger KM
中科院分区：
文献类型：
--
作者：
Eising S;Engwerda AHJ;Riedijk X;Bickelhaupt FM;Bonger KM
生物正交反应是一种不受任何生物官能团影响的选择性转化反应，广泛应用于生物大分子的化学修饰。最近，我们报道了在生物正交反电子需求Diels-Alder(IEDDA)反应中，乙烯基硼酸(VBA)与含硼吡啶基的四嗪类化合物相比没有这种取代基的四嗪类化合物具有极高的反应速率。在这一综合的实验和理论研究中，我们展示了如何通过将反应混合物中的平衡从硼酸转移到硼酸阴离子来加快VBA-四嗪连接的反应速度。量子化学激活应变分析表明，这种速率的提高是由于硼酸根阴离子优异的给电子能力的直接结果，在这种阴离子中，由于该物种的净负势，πHOMO被推到更高的能量。我们研究了几种含有潜在的VBA配位羟基取代基的四嗪类化合物的二阶速率常数。我们观察到，与没有羟基取代基的四氮杂环化合物相比，速率常数增加了几个数量级。此外，我们发现羟基取代的四嗪类化合物对VBA的选择性比常用的生物正交反应物降冰片烯更高，在水环境中也比先前研究的含吡啶取代基的四嗪类化合物更稳定。
Bioorthogonal reactions are selective transformations that are not affected by any biological functional group and are widely used for chemical modification of biomolecules. Recently, we reported that vinylboronic acids (VBAs) gave exceptionally high reaction rates in the bioorthogonal inverse electron-demand Diels–Alder (iEDDA) reaction with tetrazines bearing a boron-coordinating pyridyl moiety compared to tetrazines lacking such a substituent. In this integrated experimental and theoretical study, we show how the reaction rate of the VBA-tetrazine ligation can be accelerated by shifting the equilibrium from boronic acid to the boronate anion in the reaction mixture. Quantum chemical activation strain analyses reveal that this rate enhancement is a direct consequence of the excellent electron-donating capability of the boronate anion in which the π HOMO is pushed to a higher energy due to the net negative potential of this species. We have explored the second-order rate constants of several tetrazines containing potential VBA-coordinating hydroxyl substituents. We observed an increase in rate constants of several orders of magnitude compared to the tetrazines lacking a hydroxyl substituent. Furthermore, we find the hydroxyl-substituted tetrazines to be more selective toward VBAs than toward the commonly used bioorthogonal reactant norbornene, and more stable in aqueous environment than the previously studied tetrazines containing a pyridyl substituent.
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影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
DOI：
10.1039/c4cc06435f
发表时间：
2014-11-07
期刊：
Chemical communications (Cambridge, England)
影响因子：
--
作者：
Lee YJ;Kurra Y;Yang Y;Torres-Kolbus J;Deiters A;Liu WR
通讯作者：
Liu WR
影响因子：
4.7
作者：
Eising S;van der Linden NGA;Kleinpenning F;Bonger KM
通讯作者：
Bonger KM
影响因子：
15
作者：
Lang, Kathrin;Davis, Lloyd;Wallace, Stephen;Mahesh, Mohan;Cox, Daniel J.;Blackman, Melissa L.;Fox, Joseph M.;Chin, Jason W.
通讯作者：
Chin, Jason W.
DOI：
10.1002/cbic.201600607
发表时间：
2017-03-16
期刊：
Chembiochem : a European journal of chemical biology
影响因子：
--
作者：
Kozma E;Demeter O;Kele P
通讯作者：
Kele P