小分子生物硫醇荧光探针研究进展

半胱氨酸(Cys)、同型半胱氨酸(Hcy)和还原型谷胱甘肽(GSH)等小分子生物硫醇在人的生理活动中起着重要作用.近年来,生物和环境样品中小分子生物硫醇的检测引起科学家们极大的兴趣,生物硫醇荧光探针和比色传感器得到快速发展.根据探针与生物硫醇的反应机理,包括利用小分子生物硫醇中巯基与探针反应、巯基和氨基协同与探针反应,综述两年来生物硫醇小分子荧光探针的设计、合成与应用进展.     

一种检测生物硫醇荧光探针的合成与应用

基于硫醇诱导的迈克尔加成反应阻断探针的光诱导电子转移过程(PET)合成了一种基于氟化硼络合二吡咯甲川(Bodipy)类染料的荧光探针,该探针具有高灵敏度和选择性,可在生理条件下检测硫醇。利用核磁和高分辨质谱对探针结构进行了表征。当向探针溶液加入硫醇(0~1 000μmol/L)时,可在探针溶液的绿色光谱区域引起一个显著的荧光增强响应(增强至150倍)。同时,探针可以检测相对较低浓度的硫醇,对于含有硫醇的氨基酸(半胱氨酸、谷胱甘肽和高半胱氨酸)的检出限分别为4.5×10~(-7),1.2×10~(-7),2.1×10~(-7)mol/L。此外,相对于其他氨基酸,探针对硫醇具有较高的选择性和灵敏度。该方法成功实现了细胞内硫醇的荧光成像,证明该荧光探针在生物体系中具有潜在的应用能力。     

硫醇类荧光探针研究进展

硫醇是生物体中许多蛋白质和小分子的重要组成部分,在细胞的抗氧化系统中具有重要的作用,定量检测硫醇在生物化学和临床化学中具有重要的意义.荧光法由于其具有灵敏度高、能够实现对活体甚至单个细胞的实时可视化示踪的优点,成为目前广泛采用检测细胞内硫醇类物质的一种重要手段.本文引用文献51篇,按荧光探针与巯基作用机理的不同分类,就近年来该领域的研究进展做了比较系统的评述,并展望了此类探针的发展趋势和应用前景.     

红光/近红外光硫醇荧光探针

小分子生物硫醇,包括半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH),在生理活动中扮演了重要的角色,其浓度的异常变化常与多种疾病息息相关,因此对其进行检测就显得尤为重要.近几年来,荧光探针因具有操作简便、时空分辨率高、损伤小和可视化等优势,在硫醇的识别领域成为了研究热点之一.而在已报道的众多的硫醇荧光探针...     

基于萘酰亚胺的生物硫醇探针的合成及对含硫醇氨基酸的检测

合成了以4-羟基萘酰亚胺为荧光团,2,4-二硝基苯磺酰氧基为特异性识别基团的生物硫醇探针4-(2,4-二硝基苯磺酰氧基)-正丁基-1,8-萘酰亚胺(DNSBN).吸收光谱和荧光光谱结果表明, DNSBN对半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)3种生物硫醇分子具有高效的检测识别能力,不受其它17种天然氨基酸的干扰.同时,通过荧光滴定实验证实了此探针是一种比率型探针,555 nm处的荧光强度与溶液中的生物硫醇分子浓度在0 ~ 20 μmol/L范围内呈良好的线性关系,对Cys、Hcy和GSH的检出限(3σ)分别为25.9、92.0和77.9 nmol/L.而吸收光谱、荧光光谱和质谱表征数据显示,生物硫醇与2,4-二硝基苯磺酸酯发生亲核取代反应并导致磺酸酯的分解.随着识别基团的解离,探针分子的d-PeT (donor-excited photoinduced electron transfer) 效应被解除,并出现非常明显的比色与荧光变化.HeLa细胞成像实验表明,探针DNSBN具有良好的生物相容性,能够对细胞外源性生物硫醇分子进行检测.     

基于ESIPT机理的近红外硫醇探针及其生物成像研究

本文利用激发态分子内质子转移(ESIPT)过程可产生长波长酮式发射的特点,以HBT(2-(2’-羟基苯基)苯并噻唑)为骨架,2,4-二硝基苯磺酸基作为硫醇位点掩盖酚羟基,与丙二腈缩异佛尔酮通过共轭双键相连,构建了近红外硫醇探针SYN.该探针实现了近红外区对硫醇的定量检测,并在细胞水平上对硫醇进行了成像研究.     

基于黄酮的长波长荧光探针用于检测体外和体内生物硫醇（英文）

半胱氨酸(Cys)、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)等生物硫醇在生理和病理过程中起着至关重要的作用,尤其是GSH在肿瘤细胞中过度表达,可以作为肿瘤的生物标志物.然而,同时区分活的正常细胞和肿瘤细胞存在着困难和挑战,因此设计并合成了一种基于N,N-二甲氨基萘黄酮(3)的肉眼可见“关-开”型长波长荧光探针(4).该探针对生物硫醇具有较高的选择性和较低的检测限,机理研究表明,生物硫醇催化探针的酯键断裂,生成了强荧光的黄酮3.该探针可用于活细胞和小鼠体内生物硫醇成像,并且对正常肝细胞HL-7702和肝癌细胞HepG2进行选择性成像.     

选择性检测谷胱甘肽的荧光探针

本文设计合成了一种基于BODIPY衍生物选择性检测谷胱甘肽的比率式荧光探针1。荧光探针1中BODIPY的3位连有苯乙炔基团,5位连有咪唑盐离去基团,利用其与谷胱甘肽和半胱氨酸反应机理的不同实现了对谷胱甘肽的选择性检测。紫外可见吸收光谱和荧光光谱实验结果表明探针分子1与谷胱甘肽反应后的光谱发生明显红移,可以实现对谷胱甘肽的比率式检测。探针分子1对谷胱甘肽有极高的选择性,不受其它氨基酸尤其是半胱氨酸的干扰。荧光滴定实验表明探针分子1可实现对谷胱甘肽的定量检测,检测限为3.3×10-8 mol/L。探针分子成功地应用于活体细胞中检测谷胱甘肽。     

生物应用锌(Ⅱ)荧光探针研究进展

本文对近年来生物应用锌(Ⅱ)荧光探针研究进展进行了较详细地评述,并对其化学规律、性质和某些局限性进行了讨论。     

BODIPY-Based Fluorescent Probes for Biothiols

Fluorescent probes for biothiols have aroused increasing interest owing to their potential to enable better understanding of the diverse physiological and pathological processes related to the biothiol species. BODIPY fluorophores exhibit excellent optical properties, which can be readily tailored by introducing diverse functional units at various positions of the BODIPY core. In the present review, the development of fluorescent probes based on BODIPYs for the detection of biothiols are systematically summarized, with emphasis on the preferable detection of individual biothiols, as well as simultaneous discrimination among cysteine (Cys), homocysteine (Hcy), reduced glutathione (GSH). In addition, organelle-targeting probes for biothiols are also highlighted. The general design principles, various recognition mechanisms, and biological applications are elaboratively discussed, which could provide a useful reference to researchers worldwide interested in this area.     

荧光探针在半胱氨酸检测的应用

半胱氨酸(Cys)是三种生物硫醇之一,是20种天然氨基酸中唯一一种含还原性巯基的天然氨基酸,是组成细胞内多肽和蛋白质的基本氨基酸之一。其参与体内细胞的氧化还原调控,调节体内氧化还原平衡,维持机体正常代谢,在生理过程中发挥着至关重要的作用。然而体内的Cys浓度水平异常会引起一系列生理疾病,体内的Cys浓度作为几种疾病的生物标志物具有临床意义。因此有效地识别和检测半胱氨酸受到越来越多的研究者们的青睐。相较传统检测方法,荧光探针因其操作简单、灵敏度高、响应迅速和实时检测等优点,已被广泛用于检测生物硫醇。本文基于常见荧光团的结构性能特征,综述了近三年来检测Cys的荧光探针,重点概述了其传感机制,并对其生物应用进行了简要说明,展望了未来Cys探针的研究方向与应用前景。     

Recent Progress on NIR Fluorescent Probes for Enzymes

The majority of diseases’ biomarkers are enzymes, and the regulation of enzymes is fundamental but crucial. Biological system disorders and diseases can result from abnormal enzymatic activity. Given the biological significance of enzymes, researchers have devised a plethora of tools to map the activity of particular enzymes in order to gain insight regarding their function and distribution. Near-infrared (NIR) fluorescence imaging studies on enzymes may help to better understand their roles in living systems due to their natural imaging advantages. We review the NIR fluorescent probe design strategies that have been attempted by researchers to develop NIR fluorescent sensors of enzymes, and these works have provided deep and intuitive insights into the study of enzymes in biological systems. The recent enzyme-activated NIR fluorescent probes and their applications in imaging are summarized, and the prospects and challenges of developing enzyme-activated NIR fluorescent probes are discussed.     

生物小分子巯基化合物荧光探针研究进展

细胞内的小分子巯基化合物在诸多生理过程中扮演重要角色.分子荧光探针具有灵敏度高、选择性好、生物相容性好、实时原位监测等优点.因此,构建可以选择性检测巯基化合物的荧光探针具有重要的生物学和医学意义.根据荧光探针与巯基化合物的反应类型总结了近几年来小分子巯基化合物荧光探针的设计策略和研究进展.     

Recent Progress in Identifying Bacteria with Fluorescent Probes

The development of new techniques to rapidly and accurately detect bacteria has drawn continuous attention due to the potential threats posed by bacteria to human health and safety. Recently, a novel strategy based on fluorescent probes has drawn considerable interest for the detection of bacteria due to its high selectivity, fast response, and simple operation. In this review, we summarize the recent progress on fluorescent probes for the specific recognition and discrimination of Gram-negative and Gram-positive bacteria. In particular, we outline current design strategies, such as targeting of the differences in surface components, cell wall components, endogenous enzymes, surface charge, and hydrophobicity of various kinds of bacteria to develop various fluorescent sensors (organic small-molecule fluorescent probes, nanoprobes, and metal ion probes). We also emphasize the application of organic molecules in probe recognition elements. We hope that this review can stimulate this research area in bacterial detection and imaging in the future.     

Recent Advances in Excimer-Based Fluorescence Probes for Biological Applications

The fluorescent probe is a powerful tool for biological sensing and optical imaging, which can directly display analytes at the molecular level. It provides not only direct visualization of biological structures and processes, but also the capability of drug delivery systems regarding the target therapy. Conventional fluorescent probes are mainly based on monomer emission which has two distinguishing shortcomings in practice: small Stokes shifts and short lifetimes. Compared with monomer-based emission, excimer-based fluorescent probes have large Stokes shifts and long lifetimes which benefit biological applications. Recent progress in excimer-based fluorescent sensors (organic small molecules only) for biological applications are highlighted in this review, including materials and mechanisms as well as their representative applications. The progress suggests that excimer-based fluorescent probes have advantages and potential for bioanalytical applications.     

荧光/化学发光探针成像检测超氧阴离子自由基的研究进展

超氧阴离子自由基(O·-2)是细胞内氧气单电子还原后最先产生的一类含氧的高活性物种(活性氧,ROS),与生命过程息息相关.正常稳态浓度的O·-2起重要的信号调控作用,包括细胞的增殖、分化、自噬等.但O·-2浓度的异常,又与癌症、神经退行性疾病、糖尿病等多种疾病的发生发展密切相关.因此,监测O·-2浓度的变化对揭示相关疾病的机理具有至关重要作用.由于荧光成像检测方法具有诸多优势,发展高灵敏、高选择性检测O·-2的荧光探针成为揭示相关疾病发生发展分子机制的关键切入点.近年来,随着荧光显微技术的发展,研究者开发了多种荧光/化学发光探针,实现了对细胞及活体内O·-2水平的可视化监测.本文综述了近五年用于检测O·-2的分子探针、纳米探针、蛋白探针以及化学发光探针的研究进展,并对其发展前景进行了展望.     

光气及神经毒剂类荧光探针的研究进展

剧毒性光气、神经毒剂对社会安全和人类健康造成了极大的威胁,而传统的检测方法无法在活细胞等微环境体系中对光气、神经毒剂进行检测。荧光探针因其选择性好、灵敏度高、适合于细胞检测等优点而被广泛使用。本文主要综述了近年来在光气、神经毒剂类荧光探针领域所取得的最新研究成果,并对该领域的发展进行了展望。