Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes.
Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes.
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DOI：
10.1021/jacs.0c06725
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发表时间：
2020-11-04
影响因子：
15
通讯作者：
Schomaker JM
中科院分区：
文献类型：
--
作者：
Hu Y;Roberts JM;Kilgore HR;Mat Lani AS;Raines RT;Schomaker JM
对相互排斥的生物正交标记试剂的兴趣继续推动新化合物的设计，能够快速和可预测的反应。容易地修饰含S、N和O的环辛炔（SNO-OCT）的能力使得能够用I-III型偶极电子调谐SNO-OCT及其环加成速率。与仅基于一种特定偶极类别的优化相反，可以操纵SNO-OCT中炔的亲电性以实现不同的反应性并提供相互正交的双连接系统。与母体支架相比，二氟化SNO-OCT衍生物的反应速率显著提高，与重氮乙酰胺环加成的二阶速率常数超过5.13 M− 1 s −1。采用计算和实验研究来告知包括三个正交反应性的三重连接系统的设计。最后，极性SNO-OCT被哺乳动物细胞迅速内化，并在细胞溶质中保持活细胞标记的功能，突出了它们在体外和体内应用的潜力。
Interest in mutually exclusive pairs of bioorthogonal labeling reagents continues to drive the design of new compounds, capable of fast and predictable reactions. The ability to easily modify S-, N-, and O-containing cyclooctynes (SNO-OCTs) enables electronic tuning of SNO-OCTs and their cycloaddition rates with Type I–III dipoles. As opposed to optimizations based on just one specific dipole class, the electrophilicity of the alkynes in SNO-OCTs can be manipulated to achieve divergent reactivities and furnish mutually orthogonal dual ligation systems. Significant rate enhancements for reactions of a difluorinated SNO-OCT derivative compared to the parent scaffold were noted, with the second-order rate constant in cycloadditions with diazoacetamides exceeding 5.13 M−1s−1. Computational and experimental studies were employed to inform the design of triple ligation systems that encompass three orthogonal reactivities. Finally, polar SNO-OCTs are rapidly internalized by mammalian cells and remain functional in the cytosol for live-cell labeling, highlighting their potential for diverse in vitro and in vivo applications.
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影响因子：
15
作者：
Andersen, Kristen A.;Aronoff, Matthew R.;McGrath, Nicholas A.;Raines, Ronald T.
通讯作者：
Raines, Ronald T.
影响因子：
4
作者：
Bakkum T;van Leeuwen T;Sarris AJC;van Elsland DM;Poulcharidis D;Overkleeft HS;van Kasteren SI
通讯作者：
van Kasteren SI
影响因子：
64.5
作者：
Das DK;Govindan R;Nikić-Spiegel I;Krammer F;Lemke EA;Munro JB
通讯作者：
Munro JB
影响因子：
18.2
作者：
Devaraj NK
通讯作者：
Devaraj NK
通过超分辨率成像揭示细胞表面的碳水化合物模式
影响因子：
6.7
作者：
Chen, Junling;Gao, Jing;Wang, Hongda
通讯作者：
Wang, Hongda