背景：通过静电相互作用猝灭聚集诱导发光用于检测聚（ADP-核糖）聚合酶 1 活性。

Background-Quenched Aggregation-Induced Emission through Electrostatic Interactions for the Detection of Poly(ADP-ribose) Polymerase-1 Activity.

机构信息

Henan Province of Key Laboratory of New Optoelectronic Functional Materials, College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455000, China.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.

出版信息

Molecules. 2023 Jun 14;28(12):4759. doi: 10.3390/molecules28124759.

DOI:10.3390/molecules28124759

PMID:37375313

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10302931/

Abstract

Poly(ADP-ribose) polymerase-1 (PARP1) is a potential biomarker and therapeutic target for cancers that can catalyze the poly-ADP-ribosylation of nicotinamide adenine dinucleotide (NAD) onto the acceptor proteins to form long poly(ADP-ribose) (PAR) polymers. Through integration with aggregation-induced emission (AIE), a background-quenched strategy for the detection of PARP1 activity was designed. In the absence of PARP1, the background signal caused by the electrostatic interactions between quencher-labeled PARP1-specitic DNA and tetraphenylethene-substituted pyridinium salt (TPE-Py, a positively charged AIE fluorogen) was low due to the fluorescence resonance energy transfer effect. After poly-ADP-ribosylation, the TPE-Py fluorogens were recruited by the negatively charged PAR polymers to form larger aggregates through electrostatic interactions, thus enhancing the emission. The detection limit of this method for PARP1 detection was found to be 0.006 U with a linear range of 0.01~2 U. The strategy was used to evaluate the inhibition efficiency of inhibitors and the activity of PARP1 in breast cancer cells with satisfactory results, thus showing great potential for clinical diagnostic and therapeutic monitoring.

摘要

聚（ADP-核糖）聚合酶 1（PARP1）是一种潜在的生物标志物和治疗靶点，可催化烟酰胺腺嘌呤二核苷酸（NAD）在受体蛋白上的聚-ADP-核糖基化，形成长的聚（ADP-核糖）（PAR）聚合物。通过与聚集诱导发射（AIE）的整合，设计了一种用于检测 PARP1 活性的背景猝灭策略。在不存在 PARP1 的情况下，由于荧光共振能量转移效应，猝灭标记的 PARP1 特异性 DNA 与四苯乙烯取代的吡啶盐（TPE-Py，带正电荷的 AIE 荧光团）之间的静电相互作用导致背景信号较低。在聚 ADP-核糖基化后，TPE-Py 荧光团通过静电相互作用被带负电荷的 PAR 聚合物招募，形成更大的聚集体，从而增强了发射。该方法检测 PARP1 的检测限为 0.006 U，线性范围为 0.01~2 U。该策略用于评估抑制剂的抑制效率和乳腺癌细胞中 PARP1 的活性，结果令人满意，因此具有很大的临床诊断和治疗监测潜力。