scholarly journals Novel intramolecular photoinduced electron transfer-based probe for the Human Ether-a-go-go-Related Gene (hERG) potassium channel

The Analyst ◽  
2015 ◽  
Vol 140 (24) ◽  
pp. 8101-8108 ◽  
Author(s):  
Zhenzhen Liu ◽  
Yubin Zhou ◽  
Lupei Du ◽  
Minyong Li

A novel conformation-mediated intramolecular photoinduced electron transfer fluorogenic system based-on naphthalimide fluorophore was established for hERG potassium channel herein. After careful evaluation, probe N4 and N6 showed good activity and may have a promising application in hERG channel imaging and drug cardiotoxicity evaluation.

2020 ◽  
Vol 27 (18) ◽  
pp. 3046-3054
Author(s):  
Xiaomeng Zhang ◽  
Beilei Wang ◽  
Zhenzhen Liu ◽  
Yubin Zhou ◽  
Lupei Du

hERG (Human ether-a-go-go-related gene) potassium channel, which plays an essential role in cardiac action potential repolarization, is responsible for inherited and druginduced long QT syndrome. Recently, the Cryo-EM structure capturing the open conformation of hERG channel was determined, thus pushing the study on hERG channel at 3.8 Å resolution. This report focuses primarily on summarizing the design rationale and application of several fluorescent probes that target hERG channels, which enables dynamic and real-time monitoring of potassium pore channel affinity to further advance the understanding of the channels.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qi Li ◽  
Lijuan Chai ◽  
Gaopan Dong ◽  
Xiaomeng Zhang ◽  
Lupei Du

Three environment-sensitive probes were developed for the hERG channel based on the nitrobenzoxadiazole fluorophore herein. After careful evaluation, probes M1 and M3 were found to have a high affinity for imaging the hERG channel in the cell-based experiment. Compared with other fluorescent labeling technologies (such as fluorescent proteins), these probes afford a convenient and economical method to determine hERG channel in vitro and in cellulo. Therefore, these probes are expected to be applicable for usage in physiological and pathological studies of hERG channels and have the potential to establish a screening system for hERG channels.


2020 ◽  
Author(s):  
Rishikesh Kulkarni ◽  
Anneliese Gest ◽  
Chun Kei Lam ◽  
Benjamin Raliski ◽  
Feroz James ◽  
...  

<p>High signal-to-noise optical voltage indicators will enable simultaneous interrogation of membrane potential in large ensembles of neurons. However, design principles for voltage sensors with high sensitivity and brightness remain elusive, limiting the applicability of voltage imaging. In this paper, we use molecular dynamics (MD) simulations and density functional theory (DFT) calculations to guide the design of a bright and sensitive green-fluorescent voltage-sensitive fluorophore, or VoltageFluor (VF dye), that uses photoinduced electron transfer (PeT) as a voltage-sensing mechanism. MD simulations predict an 11% increase in sensitivity due to membrane orientation, while DFT calculations predict an increase in fluorescence quantum yield, but a decrease in sensitivity due to a decrease in rate of PeT. We confirm these predictions by synthesizing a new VF dye and demonstrating that it displays the expected improvements by doubling the brightness and retaining similar sensitivity to prior VF dyes. Combining theoretical predictions and experimental validation has resulted in the synthesis of the highest signal-to-noise green VF dye to date. We use this new voltage indicator to monitor the electrophysiological maturation of human embryonic stem cell-derived medium spiny neurons. </p>


Author(s):  
Anton J Stasyuk ◽  
Olga A. Stasyuk ◽  
Miquel Solà ◽  
Alexander Voityuk

Suitanes, a new class of two-component mechanically interlocked systems, have recently been developed. In this work, we report a detailed study of photoinduced electron transfer processes in the suit[3]anes consisting...


2021 ◽  
Vol 154 (5) ◽  
pp. 054104
Author(s):  
D. Wellnitz ◽  
G. Pupillo ◽  
J. Schachenmayer

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