Medicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125, Berlin, Germany.
State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100050, China.
Angew Chem Int Ed Engl. 2020 May 25;59(22):8512-8516. doi: 10.1002/anie.202002391. Epub 2020 Apr 16.
Herein we report the development of a turn-on lanthanide luminescent probe for time-gated detection of nitroreductases (NTRs) in live bacteria. The probe is activated through NTR-induced formation of the sensitizing carbostyril antenna and resulting energy transfer to the lanthanide center. This novel NTR-responsive trigger is virtually non-fluorescent in its inactivated form and features a large signal increase upon activation. We show that the probe is capable of selectively sensing NTR in lysates as well as in live bacteria of the ESKAPE family which are clinically highly relevant multiresistant pathogens responsible for the majority of hospital infections. The results suggest that our probe could be used to develop diagnostic tools for bacterial infections.
在此,我们报告了一种基于镧系元素发光探针的开发,该探针可用于时间门控检测活细菌中的硝基还原酶(NTR)。该探针通过 NTR 诱导的敏化咔唑天线的形成以及由此产生的能量转移到镧系元素中心而被激活。这种新型的 NTR 响应触发在其失活形式下几乎没有荧光,并且在激活时具有很大的信号增加。我们表明,该探针能够选择性地检测裂解物中的 NTR 以及临床高度相关的多药耐药病原体 ESKAPE 家族中的活细菌,这些病原体是导致大多数医院感染的主要原因。结果表明,我们的探针可用于开发用于细菌感染的诊断工具。