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Inverse electron demand Diels–Alder reactions in chemical biology
Chemical Society Reviews ( IF 46.2 ) Pub Date : 2017-06-29 00:00:00 , DOI: 10.1039/c7cs00184c
B. L. Oliveira 1, 2, 3, 4 , Z. Guo 1, 2, 3, 4 , G. J. L. Bernardes 1, 2, 3, 4, 5
Affiliation  

The emerging inverse electron demand Diels–Alder (IEDDA) reaction stands out from other bioorthogonal reactions by virtue of its unmatchable kinetics, excellent orthogonality and biocompatibility. With the recent discovery of novel dienophiles and optimal tetrazine coupling partners, attention has now been turned to the use of IEDDA approaches in basic biology, imaging and therapeutics. Here we review this bioorthogonal reaction and its promising applications for live cell and animal studies. We first discuss the key factors that contribute to the fast IEDDA kinetics and describe the most recent advances in the synthesis of tetrazine and dienophile coupling partners. Both coupling partners have been incorporated into proteins for tracking and imaging by use of fluorogenic tetrazines that become strongly fluorescent upon reaction. Selected notable examples of such applications are presented. The exceptional fast kinetics of this catalyst-free reaction, even using low concentrations of coupling partners, make it amenable for in vivo radiolabelling using pretargeting methodologies, which are also discussed. Finally, IEDDA reactions have recently found use in bioorthogonal decaging to activate proteins or drugs in gain-of-function strategies. We conclude by showing applications of the IEDDA reaction in the construction of biomaterials that are used for drug delivery and multimodal imaging, among others. The use and utility of the IEDDA reaction is interdisciplinary and promises to revolutionize chemical biology, radiochemistry and materials science.

中文翻译:

电子需求逆反应Diels–Alder反应在化学生物学中

新兴的逆电子需求Diels–Alder(IEDDA)反应因其无与伦比的动力学,出色的正交性和生物相容性而在其他生物正交反应中脱颖而出。随着新发现的亲二烯体和最佳的四嗪偶联伙伴的最新发现,现在人们已将注意力转向IEDDA方法在基础生物学,影像学和治疗学中的使用。在这里,我们审查这种生物正交反应及其在活细胞和动物研究中的有希望的应用。我们首先讨论促成快速IEDDA动力学的关键因素,并描述四嗪和亲二烯体偶联伙伴的合成中的最新进展。通过使用荧光四嗪,两个偶合伴侣已被掺入蛋白质中以进行跟踪和成像,该荧光四嗪在反应后会发出强烈的荧光。给出了此类应用的选定显着示例。即使使用低浓度的偶合剂,这种无催化剂反应的非凡的快速动力学也使其适用于使用预靶向方法进行体内放射性标记,也对此进行了讨论。最后,IEDDA反应最近已在生物正交降解中用于激活功能获得策略中的蛋白质或药物。我们通过显示IEDDA反应在构建用于药物传递和多峰成像等的生物材料中的应用来得出结论。IEDDA反应的用途和效用是跨学科的,有望改变化学生物学,放射化学和材料科学。
更新日期:2017-06-29
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