Research Progress of Fluorescent Probes for Monoamine Oxidases

Xiao-peng WANG; Yong-dong LI; Jian-guo WANG

doi:10.37188/CJL.20210086

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Research Progress of Fluorescent Probes for Monoamine Oxidases

Invited Review | Updated：2021-07-22

- Research Progress of Fluorescent Probes for Monoamine Oxidases Enhanced Publication
- Chinese Journal of Luminescence Vol.42, Issue 7, (2021)
- Affiliations：
  
  Key Laboratory of Organo-pharmaceutical Chemistry, College of Chemistry and Chemical Engineering, Gannan Normal University,Ganzhou,China,341000;Inner Mongolia Key Laboratory of Fine Organic Synthesis, College of Chemistry and Chemical Engineering, Inner Mongolia University,Hohhot,China,010021
- Author bio：
- Funds：
  
  National Natural Science Foundation of China(21871060);the Natural Science Foundation of Inner Mongolia Autonomous Region of China(2020JQ02;2020MS02004);the Natural Science Foundation of Jiangxi Province(20192BCBL23013);Grassland Talent Program of Inner Mongolia Autonomous Region of China
- DOI：10.37188/CJL.20210086 CLC： O482.31
- Published：01 July 2021，
  
  Received：12 March 2021，
  
  Revised：02 April 2021，
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Xiao-peng WANG, Yong-dong LI, Jian-guo WANG. Research Progress of Fluorescent Probes for Monoamine Oxidases. [J]. Chinese Journal of Luminescence 42(7):938-952(2021)
DOI：

Xiao-peng WANG, Yong-dong LI, Jian-guo WANG. Research Progress of Fluorescent Probes for Monoamine Oxidases. [J]. Chinese Journal of Luminescence 42(7):938-952(2021) DOI： 10.37188/CJL.20210086.

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"lang": "zh", "text": [ "王建国(1982-)，男，内蒙古兴和人，博士，研究员，博士研究生导师，2014年于中国科学院化学研究所获得博士学位，主要从事离子-π型有机光电功能材料(包括发光材料机理、有机室温磷光材料的开发与应用及光动力诊疗等)的研究。E-mail: wangjg@iccas.ac.cn" ], "graphic": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351682&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351689&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351694&type=" } ], "data": [ [ { "name": "text", "data": "王建国" }, { "name": "text", "data": "(1982-)，男，内蒙古兴和人，博士，研究员，博士研究生导师，2014年于中国科学院化学研究所获得博士学位，主要从事离子-π型有机光电功能材料(包括发光材料机理、有机室温磷光材料的开发与应用及光动力诊疗等)的研究。E-mail: " }, { "name": "text", "data": "wangjg@iccas.ac.cn" } ] ] } ], "email": "wangjg@iccas.ac.cn", "deceased": false } ], "aff": [ { "id": "aff1", "intro": [ { "lang": "zh", "label": "1", "text": "赣南师范大学化学化工学院　江西省有机药物化学重点实验室，江西　赣州　 341000", "data": [ { "name": "text", "data": "赣南师范大学化学化工学院　江西省有机药物化学重点实验室，江西　赣州　 341000" } ] }, { "lang": "en", "label": "1", "text": "Key Laboratory of Organo-pharmaceutical Chemistry, College of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, China", "data": [ { "name": "text", "data": "Key Laboratory of Organo-pharmaceutical Chemistry, College of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou 341000, China" } ] } ] }, { "id": "aff2", "intro": [ { "lang": "zh", "label": "2", "text": "内蒙古大学化学化工学院　内蒙古精细有机合成重点实验室，内蒙古　呼和浩特　 010021", "data": [ { "name": "text", "data": "内蒙古大学化学化工学院　内蒙古精细有机合成重点实验室，内蒙古　呼和浩特　 010021" } ] }, { "lang": "en", "label": "2", "text": "Inner Mongolia Key Laboratory of Fine Organic Synthesis, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China", "data": [ { "name": "text", "data": "Inner Mongolia Key Laboratory of Fine Organic Synthesis, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot 010021, China" } ] } ] } ] }, "abstracts": [ { "lang": "zh", "data": [ { "name": "p", "data": [ { "name": "text", "data": "单胺氧化酶(Monoamine oxidases,MAOs)是一种膜结合的线粒体酶，通过催化氧化及脱氨反应来维持神经递质和其他生物胺在生物系统中的稳态。MAOs功能障碍与许多神经和精神疾病密切相关，因此，监测MAOs的活性及表达水平，对深入理解其生理功能及相关疾病的临床诊断都具有十分重要的意义。荧光探针具有原位、无创、可实时成像等优势，是准确监测MAOs活性的一种有效方法。本文综述了近年来MAOs荧光探针的研究进展，阐述了这些荧光探针在MAOs相关疾病诊断及治疗中的应用。" } ] } ] }, { "lang": "en", "data": [ { "name": "p", "data": [ { "name": "text", "data": "Monoamine oxidases(MAOs) are a family of membrane-bound mitochondrial enzymes that play important roles in maintaining the homeostasis of neurotransmitters and other bioamines in the biological system through catalytic oxidation and deamination. The dysfunction of MAOs is closely related to many neurological and psychiatric disorders. Thus, monitoring the activity/level of MAOs is of great significance for deeply understanding their physiological functions and for clinical diagnosis of MAOs-related diseases. Fluorescent probes with the ability of" }, { "name": "italic", "data": [ { "name": "text", "data": "in situ" } ] }, { "name": "text", "data": ", noninvasive and real-time imaging provide an effective method to accurately detect MAOs activity. In this review, the research progress of fluorescent probes for MAOs in recent years and their applications for the diagnosis and therapy of MAOs-related diseases are reviewed." } ] } ] } ], "keyword": [ { "lang": "zh", "data": [ [ { "name": "text", "data": "单胺氧化酶" } ], [ { "name": "text", "data": "荧光探针" } ], [ { "name": "text", "data": "疾病诊断" } ], [ { "name": "text", "data": "抑制剂" } ], [ { "name": "text", "data": "生物成像" } ] ] }, { "lang": "en", "data": [ [ { "name": "text", "data": "monoamine oxidase" } ], [ { "name": "text", "data": "fluorescent probes" } ], [ { "name": "text", "data": "disease diagnosis" } ], [ { "name": "text", "data": "inhibitor" } ], [ { "name": "text", "data": "bioimaging" } ] ] } ], "highlights": [], "body": [ { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "1　引言" } ], "level": "1", "id": "s1" } }, { "name": "p", "data": [ { "name": "text", "data": "单胺氧化酶(MAOs)是一类黄素酶，主要在线粒体外膜上分布，可催化胺类底物氧化成酮或醛，并产生过氧化氢和氨作为副产物" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "1", "type": "bibr", "rid": "R1", "data": [ { "name": "text", "data": "1" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "3", "type": "bibr", "rid": "R3", "data": [ { "name": "text", "data": "3" } ] } } ], "rid": [ "R1", "R2", "R3" ], "text": "1-3", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。MAOs有两种亚型:MAO-A和MAO-B。它们虽然有70%的序列同源性" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "4", "type": "bibr", "rid": "R4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "7", "type": "bibr", "rid": "R7", "data": [ { "name": "text", "data": "7" } ] } } ], "rid": [ "R4", "R5", "R6", "R7" ], "text": "4-7", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，但在许多方面存在差异，包括在细胞和组织中的分布、底物的特异性以及功能上的差异。MAO-A主要分布于儿茶酚胺能神经元，代谢多种不同的神经递质，并可被氯吉兰(Clorgyline,CL)选择性抑制(" }, { "name": "xref", "data": { "text": "图1", "type": "fig", "rid": "F1", "data": [ { "name": "text", "data": "图1" } ] } }, { "name": "text", "data": ")。MAO-B主要存在于星形胶质细胞(某些情况下还存在于血清素能神经元中)，作用于多巴胺(DA)和β-苯乙胺，可被优降宁(Pargyline,PA)、雷沙吉兰 (Rasagiline,RA)、司来吉兰(Selegiline,SE)选择性抑制。虽然MAO-A和MAO-B对不同底物的选择性和特异性不同，但是它们在维持生物胺代谢稳态中共同发挥着至关重要的作用。MAOs的过度激活会增加神经毒性化合物的产生。MAOs功能障碍可引起阿尔茨海默病(AD)、帕金森病(PD)等多种神经和精神疾病" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "8", "type": "bibr", "rid": "R8", "data": [ { "name": "text", "data": "8" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "14", "type": "bibr", "rid": "R14", "data": [ { "name": "text", "data": "14" } ] } } ], "rid": [ "R8", "R9", "R10", "R11", "R12", "R13", "R14" ], "text": "8-14", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。因此，设计开发可靠的、特异性检测这两种同工酶的方法对于深入理解它们在生物系统中的功能及MAOs相关疾病的临床诊断和治疗都具有重要意义。" } ] }, { "name": "fig", "data": { "id": "F1", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图1" } ], "title": [ { "name": "text", "data": "几种常见的单胺氧化酶抑制剂" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.1" } ], "title": [ { "name": "text", "data": "Common inhibitors for MAOs" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351702&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351712&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351708&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "迄今为止，科学家已经建立了多种检测MAOs活性的方法，如光谱法、生物发光法、酶联免疫分析法、放射性标记法及荧光探针法等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "15", "type": "bibr", "rid": "R15", "data": [ { "name": "text", "data": "15" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "18", "type": "bibr", "rid": "R18", "data": [ { "name": "text", "data": "18" } ] } } ], "rid": [ "R15", "R16", "R17", "R18" ], "text": "15-18", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。其中，荧光探针法具有检测成本低、方便快捷、特异性强、灵敏度高、非侵入性等优点，非常适用于对活细胞或活体小动物中的生物酶进行实时无损成像" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "19", "type": "bibr", "rid": "R19", "data": [ { "name": "text", "data": "19" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "24", "type": "bibr", "rid": "R24", "data": [ { "name": "text", "data": "24" } ] } } ], "rid": [ "R19", "R20", "R21", "R22", "R23", "R24" ], "text": "19-24", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。目前，MAOs荧光探针的开发已经取得了非常多的成果，根据其作用机制，我们把这些荧光探针分为结合型和反应型两大类，如" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "所示。本篇综述对这两大类用于检测MAOs的荧光探针进行了系统详细的介绍，阐述了其在MAOs相关疾病诊断和治疗中的应用，并进一步对MAOs荧光探针的发展前景进行了展望。" } ] }, { "name": "fig", "data": { "id": "F2", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图2" } ], "title": [ { "name": "text", "data": "单胺氧化酶荧光探针示意图" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.2" } ], "title": [ { "name": "text", "data": "Schematic diagram of fluorescent probes for monoamine oxidase" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351721&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351731&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351724&type=" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2　单胺氧化酶荧光探针" } ], "level": "1", "id": "s2" } }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.1　结合型单胺氧化酶荧光探针" } ], "level": "2", "id": "s2a" } }, { "name": "p", "data": [ { "name": "text", "data": "结合型单胺氧化酶荧光探针一般是根据酶的抑制剂或天然底物与单胺氧化酶的高亲和力设计而成的，一般包括三部分:(1)能够通过共价键或非共价键与单胺氧化酶的活性位点作用的结合基团;(2)可视化的荧光基团;(3)防止荧光基团在酶的活性位点产生较大位阻效应的链接基团。2012年，朱勍课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "25", "type": "bibr", "rid": "R25", "data": [ { "name": "text", "data": "25" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "将2-烷氨基乙酰胺引入荧光素中合成了一个结合型单胺氧化酶荧光探针1，为了使荧光素远离MAOs结合位点，他们在荧光素部分和2-烷氨基乙酰胺之间引入了一个长度为6个碳原子的烷基链。探针1可有效与MAO-A和MAO-B结合，并抑制其活性，" }, { "name": "inlineformula", "data": [ { "name": "math", "data": { "graphicsData": { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351735&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351745&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351740&type=" } } } ] }, { "name": "text", "data": "(酶活性被抑制一半时的抑制剂浓度)值分别为35.1 μmol/L和150.8 μmol/L。探针1可用于在活细胞内标记MAOs，在细胞内产生明显的荧光发射。如" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "所示，探针1对MAOs的标记过程主要分为三步:(1) 2-烷氨基乙酰胺与MAOs结合形成稳定的化合物b;(2)在碱的作用下，被活化的黄素(Flavin)促使b发生氧化脱氨反应，生成亚胺基化合物c;(3)化合物c被亲核性的巯基进攻生成d。荧光探针1可以非常方便地对MAOs进行荧光成像，并且也是监控MAOs相关疾病进程的一个非常有前景的选择。" } ] }, { "name": "fig", "data": { "id": "F3", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图3" } ], "title": [ { "name": "text", "data": "(a)探针1的结构;(b)探针1在MCF-7细胞中的荧光成像;(c)探针1共价键合标记MAO的机理。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.3" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 1. (b)Fluorescence microscopy of MCF-7 cells stained with probe 1. (c)Proposed mechanism of covalent labeling of MAO with reaction-based fluorescent probe 1." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351751&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351765&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351756&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "同年，Breinbauer等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "26", "type": "bibr", "rid": "R26", "data": [ { "name": "text", "data": "26" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "根据MAOs抑制剂优降宁和司来吉兰的结构设计合成了一系列结合型MAOs荧光探针2~7 (P1-P6)，如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "所示。体外实验结果表明，含甲基取代的叔胺结构的探针2、4、6能够有效地与MAOs结合，而不含甲基取代的叔胺结构的3、5、7对MAOs的标记能力很弱。标记的机理是:探针2、4、6叔胺结构的N可被MAOs氧化，进而辅酶FAD中的N原子可与氧化的探针发生Michael加成反应，实现探针对MAOs的标记。探针2和4可用于研究活细胞或组织中MAOs的蛋白质活性表达谱，因其出色的选择性有望用于研究临床药物司来吉兰的脱靶作用。这是文献报道的第一个可用于标记蛋白质活性表达谱的结合型小分子荧光探针。" } ] }, { "name": "fig", "data": { "id": "F4", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图4" } ], "title": [ { "name": "text", "data": "探针2~7的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.4" } ], "title": [ { "name": "text", "data": "Structures of the probe 2-7" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351772&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351784&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351777&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "内源性MAO-A表达量比较高时，探针4对MAO-B的特异性较弱。另外，探针4虽然能够穿透细胞膜进入细胞，但是其发光波长较短，并不适合在细胞或者组织中对MAOs进行荧光成像。2015年，新加坡国立大学姚少钦" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "27", "type": "bibr", "rid": "R27", "data": [ { "name": "text", "data": "27" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "课题组首次报道了兼具蛋白质表达谱原位标记和活细胞内MAO-B荧光成像能力的小分子荧光探针8(M2)，如" }, { "name": "xref", "data": { "text": "图5(a)", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5(a)" } ] } }, { "name": "text", "data": "所示。探针8对MAO-B具有较强的特异性，即使在MAO-A过表达的情况下，也能保持对MAO-B的高特异性，探针8对MAO-B和MAO-A的" }, { "name": "inlineformula", "data": [ { "name": "math", "data": { "graphicsData": { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351789&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351802&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351796&type=" } } } ] }, { "name": "text", "data": "分别为10.8 nmol/L和379 nmol/L。探针8可采用原位标记蛋白质表达谱或活细胞成像的方式报告内源性MAO-B的活性，并且能够用于揭示帕金森病动物模型中MAO-B表达水平与多巴胺能神经元内稳态之间的关系。" } ] }, { "name": "fig", "data": { "id": "F5", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图5" } ], "title": [ { "name": "text", "data": "(a)探针8的结构;(b)探针9的结构;(c)探针9对C4-2B前列腺癌荷瘤小鼠肿瘤的治疗效果;(d)探针9在荷瘤小鼠体内前列腺肿瘤的近红外荧光成像。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.5" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 8. (b)Structure of the probe 9. (c)9 inhibits the growth of C4-2B tumor xenografts in mice. (d)NIR fluorescence imaging of probe 9 " }, { "name": "italic", "data": [ { "name": "text", "data": "in vivo." } ] } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351807&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351816&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351813&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "开发具有肿瘤靶向能力的高效抗癌试剂是现代肿瘤学研究的重要方向之一。近期研究结果表明，MAO-A水平升高与前列腺癌患者预后较差具有一定的相关性。MAO-A可诱导上皮间质转化，并通过产生大量的活性氧物种(ROS)放大肿瘤的乏氧效应" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "28", "type": "bibr", "rid": "R28", "data": [ { "name": "text", "data": "28" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "31", "type": "bibr", "rid": "R31", "data": [ { "name": "text", "data": "31" } ] } } ], "rid": [ "R28", "R29", "R30", "R31" ], "text": "28-31", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。因此，开发能够特异性地靶向肿瘤组织的MAO-A抑制剂对于这类癌症患者具有重要的意义。Shih等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "将MAO-A抑制剂氯吉兰共价键合到近红外花菁染料上，合成了一个兼具荧光成像和抗癌能力的荧光探针9(NMI)，如" }, { "name": "xref", "data": { "text": "图5(b)~(d)", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5(b)~(d)" } ] } }, { "name": "text", "data": "所示。探针9可抑制MAO-A的活性，" }, { "name": "inlineformula", "data": [ { "name": "math", "data": { "graphicsData": { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351822&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351832&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351826&type=" } } } ] }, { "name": "text", "data": "值为(3.8±0.3) μmol/L，可抑制前列腺癌细胞增殖及集落形成，降低转移率和侵袭性。在小鼠前列腺癌异种移植物中，探针9可靶向肿瘤，而不在正常组织中富集，可有效降低肿瘤负荷。通过分析发现，肿瘤标本中Ki-67" }, { "name": "sup", "data": [ { "name": "text", "data": "+" } ] }, { "name": "text", "data": "细胞和CD31" }, { "name": "sup", "data": [ { "name": "text", "data": "+" } ] }, { "name": "text", "data": "细胞明显减少，说明癌细胞增殖和血管生成变慢，同时肿瘤样本中M30" }, { "name": "sup", "data": [ { "name": "text", "data": "+" } ] }, { "name": "text", "data": "细胞增多，说明细胞凋亡加快。这使得探针9成为一种诊断和治疗前列腺癌的新药物。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "聚集诱导发光(Aggregation-induced emission,AIE)概念自2001年提出以来，受到了人们的广泛关注，近年来更是取得了长足的进展。AIE分子具有在溶液中不发光、而在聚集态或固态时具有强发光的独特发光性质，可有效解决传统发光团因聚集导致的荧光猝灭(Aggregation-caused quenching,ACQ)问题。此外，AIE分子通常还具有发光强、光稳定性好及Stokes位移大等性质，因此，AIE材料已经在化学/生物传感" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "33", "type": "bibr", "rid": "R33", "data": [ { "name": "text", "data": "33" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、生物成像" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "34", "type": "bibr", "rid": "R34", "data": [ { "name": "text", "data": "34" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "36", "type": "bibr", "rid": "R36", "data": [ { "name": "text", "data": "36" } ] } } ], "rid": [ "R34", "R35", "R36" ], "text": "34-36", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、工程材料等领域" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "37", "type": "bibr", "rid": "R37", "data": [ { "name": "text", "data": "37" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "47", "type": "bibr", "rid": "R47", "data": [ { "name": "text", "data": "47" } ] } } ], "rid": [ "R37", "R38", "R39", "R40", "R41", "R42", "R43", "R44", "R45", "R46", "R47" ], "text": "37-47", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "取得了丰富的研究进展。其中，四苯乙烯(TPE)更是作为AIE材料的明星分子被广泛研究。具有AIE性质的荧光团(AIEgens)已经成为开发新型生物传感器的一个强大而通用的平台。朱勍课题组联合新加坡国立大学刘斌教授团队" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "48", "type": "bibr", "rid": "R48", "data": [ { "name": "text", "data": "48" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计并合成了一系列基于TPE的荧光探针，用于检测MAOs，如" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "所示。这些探针是基于探针与蛋白质之间的特定相互作用而设计的，N-甲基苯基吡啶及其类似物是MAO-A和MAO-B的抑制剂，对MAO-A和MAO-B都有很高的亲和力，TPE作为4-位苯基吡啶的大取代基，有望使探针对MAO-A有更强的选择性。在所开发的6种探针中，探针11在加入MAOs后显示出明显的荧光增强，并对MAO-A表现出较高的特异性。探针11可作为MAO-A的非竞争抑制剂，" }, { "name": "italic", "data": [ { "name": "text", "data": "K" } ] }, { "name": "sub", "data": [ { "name": "text", "data": "i" } ] }, { "name": "text", "data": "(抑制常数)值为17.1 μmol/L。并且，探针11可以靶向线粒体，特异性地监控MCF-7细胞中的MAO-A活性。" } ] }, { "name": "fig", "data": { "id": "F6", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图6" } ], "title": [ { "name": "text", "data": "AIE型MAO荧光探针10~15的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.6" } ], "title": [ { "name": "text", "data": "Structures of the AIE-active fluorescent probes 10-15 for MAOs" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351837&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351844&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351839&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "双光子荧光成像技术因其深的组织穿透深度可有效提高成像质量，其近红外较弱的激发能量也能有效地降低不必要的组织损伤。2019年，Kim等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "49", "type": "bibr", "rid": "R49", "data": [ { "name": "text", "data": "49" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计合成了一个双光子结合型MAOs荧光探针16(PCP-1)，如" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "所示。他们将MAO-A选择性抑制剂吗氯贝胺(moclobemide)共价键合到双光子荧光团上，以此来提高成像时的激发光穿透深度。探针16可特异性地与前列腺癌中过表达的MAO-A结合，产生强荧光发射，由此可区分MAO-A过表达的前列腺癌细胞和其他MAO-A低表达的癌细胞。同时，通过抑制MAO-A的活性，探针16可以有效抑制前列腺癌细胞的生长、增殖及转移，非常有望作为进一步的体内成像试剂，设计成靶向前列腺癌治疗药物。" } ] }, { "name": "fig", "data": { "id": "F7", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图7" } ], "title": [ { "name": "text", "data": "(a)探针16的结构;(b)探针16孵育LNCap细胞后细胞迁移24 h后的结果;(c)Western blot法分析探针16处理后的上皮向间质转化(EMT)相关标志物E-cadherin、N-cadherin和Twist-1的表达情况。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.7" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 16. (b)Cell migration assay in LNCap cells incubated with the probe 16 and then the images were obtained for 24 h. (c)Expression of the epithelial to mesenchymal transition(EMT)-related markers, E-cadherin, N-cadherin, and Twist-1 were observed after 16 treatment using Western blot assay." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351847&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351858&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351853&type=" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2　反应型单胺氧化酶荧光探针" } ], "level": "2", "id": "s2b" } }, { "name": "p", "data": [ { "name": "text", "data": "结合型MAOs荧光探针在应用于活体成像时往往难以准确设计“点亮型”探针，因此，研究相对较少，发展也相对缓慢。而相对于结合型MAOs荧光探针，反应型MAOs荧光探针则能从根本上克服这一缺陷。反应型MAOs荧光探针通常是根据MAOs与底物的特异性催化反应来设计的。将酶特异性的底物与荧光发色团共价键合，当MAOs与荧光探针的底物部分反应后，导致探针结构改变，就能够有效地引起荧光团的发光颜色或强度变化，从而起到检测和监控酶活性的作用。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "早在20世纪末，科学家们就利用MAOs与底物的特异性反应设计合成了能够检测MAOs的荧光探针，如" }, { "name": "xref", "data": { "text": "图8(a)", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8(a)" } ] } }, { "name": "text", "data": "所示。1996年，Silverman等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "50", "type": "bibr", "rid": "R50", "data": [ { "name": "text", "data": "50" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "报道了利用E-2,5-二甲氧基桂皮胺盐酸盐(探针" } ] }, { "name": "fig", "data": { "id": "F8", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图8" } ], "title": [ { "name": "text", "data": "探针17(a)和18(b)对MAO-B的响应机制" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.8" } ], "title": [ { "name": "text", "data": "Response mechanism ofthe probe 17(a) and 18(b) MAOs" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351864&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351874&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351869&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "17)来直接检测MAO-B的活性，探针17具有强荧光，在MAO-B的氧化作用下，氨基被氧化为醛基，荧光减弱，因此可以通过连续监测荧光强度随时间的减弱来快速有效地测定MAO-B的活性。1997年，Panchuk-Voloshina等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "51", "type": "bibr", "rid": "R51", "data": [ { "name": "text", "data": "51" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "采用一种间接的方法来检测MAOs的活性，如" }, { "name": "xref", "data": { "text": "图8(b)", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8(b)" } ] } }, { "name": "text", "data": "所示，他们利用商业化过氧化氢荧光探针18(Ample" }, { "name": "inlineformula", "data": [ { "name": "math", "data": { "graphicsData": { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351879&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351890&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351883&type=" } } } ] }, { "name": "text", "data": " Red)在辣根过氧化物酶(HRP)存在的条件下通过监控MAOs催化氧化苯乙胺生成的双氧水副产物的方法来间接测定MAOs的活性，这种方法可检测低至1.2×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-5" } ] }, { "name": "text", "data": " U/mL的MAO-B，并可在牛脑组织匀浆中检测MAO-A和MAO-B。然而，探针17的激发和发射波长太短，无法避免生物组织自发荧光的干扰，而后者为间接测定法。因此，这两种方法均不适用于活细胞或活体组织、小动物中MAOs的检测。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "为了扩展MAOs荧光探针的应用范围，21世纪初以来，科学家们进行了大量的探索和不断的努力，成功开发了众多性能优异的MAOs荧光探针，不断延长其激发和发射波长，并将其用于更为复杂的生物体系中。本研究进展中，我们根据这些探针对MAO-A和MAO-B的特异性进行分类详细介绍。" } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2.1　检测MAOs总量的荧光探针" } ], "level": "3", "id": "s2b1" } }, { "name": "p", "data": [ { "name": "text", "data": "相较于能够特异性检测MAO-A或MAO-B的荧光探针，能够检测MAOs总量的荧光探针设计更为简单方便，并且也更容易商业化。2007年，Chang课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "52", "type": "bibr", "rid": "R52", "data": [ { "name": "text", "data": "52" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "根据MAOs氧化氨基及随后的β-消除反应设计合成了两个反应型MAOs荧光探针19和20，如" }, { "name": "xref", "data": { "text": "图9(a)", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9(a)" } ] } }, { "name": "text", "data": "所示。探针19和20的激发和发射均位于可见光区域，与MAOs反应后，荧光大幅增强，因此可用于活细胞内MAOs的检测。" } ] }, { "name": "fig", "data": { "id": "F9", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图9" } ], "title": [ { "name": "text", "data": "(a)探针19和20的结构及其对MAO的响应机制;(b)探针21~23的结构以及对MAOs的响应机制;(c)探针24对MAOs的响应机制。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.9" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 19-20 and their response mechanism to MAOs. (b)Structure of the probe 21-23 and their response mechanism to MAOs. (c)Response mechanism of the probe 24 to MAOs." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351894&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351904&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351899&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "为了避免细胞和组织自发荧光的干扰，2010年，Xing课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "53", "type": "bibr", "rid": "R53", "data": [ { "name": "text", "data": "53" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "基于6-氯-2-(5-氯-2-羟基苯基)-4(3H)-喹唑酮(HPQ)衍生物设计合成了一系列反应型MAOs荧光探针21~23，如" }, { "name": "xref", "data": { "text": "图9(b)", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9(b)" } ] } }, { "name": "text", "data": "所示。HPQ衍生物一般不溶于水，在固态具有较强的荧光，具有较大的Stokes位移(110 nm)，能够有效避免细胞和组织自身发光的干扰，因此备受关注。该课题组将氨丙基基团共价键合到HPQ分子中2-羟基上，有效地猝灭了HPQ分子的荧光。当MAOs与探针反应后，氨基被氧化并随后发生自发的β-消除反应，生成绿色荧光的HPQ沉淀物，可用于活细胞或组织内MAOs的实时荧光检测。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "张德清课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "54", "type": "bibr", "rid": "R54", "data": [ { "name": "text", "data": "54" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计合成了具有AIE特性的反应型MAOs荧光探针24，如" }, { "name": "xref", "data": { "text": "图9(b)", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9(b)" } ] } }, { "name": "text", "data": "所示。庚胺在MAOs的作用下被转化为庚醛，庚醛与HS" }, { "name": "inlineformula", "data": [ { "name": "math", "data": { "graphicsData": { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351907&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351916&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351911&type=" } } } ] }, { "name": "text", "data": "反应可生成中间体(化合物2)，而探针24可在中间体诱导下发生聚集，从而荧光增强。该体系对MAO-B的检测限为0.25 mg/mL，可用于MAO-B活性分析及相关抑制剂筛选。然而，该体系不能用于活细胞或组织内MAOs活性的实时监测。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "朱勍课题组联合新加坡国立大学姚少钦课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "55", "type": "bibr", "rid": "R55", "data": [ { "name": "text", "data": "55" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "报道了第一个基于荧光共振能量转移机制(FRET)设计的反应型MAOs小分子探针25a和25b，如" }, { "name": "xref", "data": { "text": "图10", "type": "fig", "rid": "F10", "data": [ { "name": "text", "data": "图10" } ] } }, { "name": "text", "data": "所示。该体系选用荧光素作为FRET的给体单元，选用具有长发射波长的Cy3作为能量受体单元，分别选用1-甲基-1,2,3,6-四氢吡啶及3-氨基丙基作为MAOs的响应单元。实验结果表明，探针25a对MAOs的响应更加灵敏，并成功用于活细胞中MAOs活性的检测。同年，朱勍课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "56", "type": "bibr", "rid": "R56", "data": [ { "name": "text", "data": "56" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "还设计合成了另外一系列荧光素MAOs荧光探针26a~26d，如" }, { "name": "xref", "data": { "text": "图10", "type": "fig", "rid": "F10", "data": [ { "name": "text", "data": "图10" } ] } }, { "name": "text", "data": "所示。其中26a显示出对MAOs的高活性，并可用于活细胞内MAOs的活性检测。" } ] }, { "name": "fig", "data": { "id": "F10", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图10" } ], "title": [ { "name": "text", "data": "探针25~28的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.10" } ], "title": [ { "name": "text", "data": "Structures of the probe 25-28" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351919&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351936&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351924&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "发射波长位于650 nm以上的近红外荧光探针能够有效避免生物组织自发荧光的干扰，降低光对细胞和组织的损伤作用，并增加组织穿透深度。为此，2016年，Li等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "57", "type": "bibr", "rid": "R57", "data": [ { "name": "text", "data": "57" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计合成了两个具有近红外发射的MAOs荧光探针27和28，如" }, { "name": "xref", "data": { "text": "图10", "type": "fig", "rid": "F10", "data": [ { "name": "text", "data": "图10" } ] } }, { "name": "text", "data": "所示。这两个探针对MAOs都具有较高的灵敏度和特异性，Stokes位移可达227 nm，其中探针27对MAO-B响应的检测限为1.2 mg/mL。并且27具有低细胞毒性，可用于检测HeLa细胞和HepG2细胞内MAOs的活性。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "近年来，随着MAOs荧光探针技术的不断进步，人们越来越多地运用荧光成像来直观地观察和研究MAOs与相关疾病的形成过程。2016年，Ahn课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "58", "type": "bibr", "rid": "R58", "data": [ { "name": "text", "data": "58" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "利用双光子荧光探针29研究帕金森综合症中Aβ斑块的形成，监控帕金森综合症的进展过程。如" }, { "name": "xref", "data": { "text": "图11", "type": "fig", "rid": "F11", "data": [ { "name": "text", "data": "图11" } ] } }, { "name": "text", "data": "所示，探针29可同时监测患帕金森综合症小鼠脑部MAOs的水平及Aβ斑块形成之间的关系。实验结果表明，随着小鼠鼠龄的增加，小鼠脑部Aβ斑块中及斑块外部的荧光强度均不断增强，表明小鼠帕金森综合症主要经历3个进程:从出生到三月龄的缓慢启动阶段、随后的侵袭阶段及9月龄后的饱和阶段。该探针解释了MAOs水平与小鼠帕金森综合症进展之间的密切关系，进一步证明MAOs可作为帕金森综合症的生物标志物。" } ] }, { "name": "fig", "data": { "id": "F11", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图11" } ], "title": [ { "name": "text", "data": "(a)探针29的结构及其对MAOs的响应机制;(b)转基因小鼠和健康小鼠额皮质区荧光成像;(c)图(b)中Aβ斑块及背景的平均发光强度关系图;(d)背景荧光强度与斑块体积关系图。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.11" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 29 and its response mechanism to MAOs. (b)" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " fluorescence images of the frontal cortex region of transgenic and healthy mice. (c)Plots of the average fluorescence intensity of Aβ plaques and background images in panel (b), respectively. (d)A plot of the background fluorescence intensity " }, { "name": "italic", "data": [ { "name": "text", "data": "versus" } ] }, { "name": "text", "data": " the plaque volume." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351941&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351952&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351946&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "2019年，湖南大学张晓兵课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "59", "type": "bibr", "rid": "R59", "data": [ { "name": "text", "data": "59" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计合成了一种“双重锁定”的分子探针30(NML)用于精确成像及肝病区分，如" }, { "name": "xref", "data": { "text": "图12", "type": "fig", "rid": "F12", "data": [ { "name": "text", "data": "图12" } ] } }, { "name": "text", "data": "所示，探针30的第一把钥匙是亮氨酸氨肽酶(LAP)，第二把钥匙是MAOs。只有当两把钥匙同时存在，相继与探针30反应后才能释放出强荧光的NF。与单重锁定的探针相比，探针30在药物诱导肝脏损伤的荧光成像中表现出更高的准确性。血清测定结果显示，探针30在小鼠模型中能有效区分药物诱导肝脏损伤及CCl" }, { "name": "sub", "data": [ { "name": "text", "data": "4" } ] }, { "name": "text", "data": "导致的肝硬化。并且，探针30还能用于准确区分不同肝病患者的血清样本，在不同肝脏疾病的诊断中具有广阔的应用前景。" } ] }, { "name": "fig", "data": { "id": "F12", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图12" } ], "title": [ { "name": "text", "data": "探针30的结构及其对MAOs的响应机制" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.12" } ], "title": [ { "name": "text", "data": "Structure of the probe 30 and the response mechanism to MAOs" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351956&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351964&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351960&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "前述反应型MAOs荧光探针大多是采用3-氨基丙基或1-甲基-1,2,3,6-四氢吡啶作为响应基团的。2020年，川北医学院的刘军课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "60", "type": "bibr", "rid": "R60", "data": [ { "name": "text", "data": "60" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "设计合成了以哌嗪为响应基团的反应型MAOs荧光探针31和32，如" }, { "name": "xref", "data": { "text": "图13", "type": "fig", "rid": "F13", "data": [ { "name": "text", "data": "图13" } ] } }, { "name": "text", "data": "所示。其中探针32对MAOs的响应更灵敏，并且可实时响应，不需要孵育，如此迅速的响应使得该探针显示出比以往报道的MAOs荧光探针独特的优越性。同年，该课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "61", "type": "bibr", "rid": "R61", "data": [ { "name": "text", "data": "61" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "基于对MAOs类似的检测机理，还设计合成了三芳基硼烷类MAOs双光子荧光探针33~35，如" }, { "name": "xref", "data": { "text": "图14", "type": "fig", "rid": "F14", "data": [ { "name": "text", "data": "图14" } ] } }, { "name": "text", "data": "所示。其中探针34对MAOs的响应最佳，并可区分MAOs过表达的癌细胞与MAOs低表达的其他细胞。" } ] }, { "name": "fig", "data": { "id": "F13", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图13" } ], "title": [ { "name": "text", "data": "(a)探针31和32的结构;(b)探针32对MAOs的识别机理。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.13" } ], "title": [ { "name": "text", "data": "(a)Structures of the probe 31 and 32. (b)Response mechanism of the probe 32 to MAOs." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351967&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351972&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351970&type=" } ] } }, { "name": "fig", "data": { "id": "F14", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图14" } ], "title": [ { "name": "text", "data": "探针33~35的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.14" } ], "title": [ { "name": "text", "data": "Structures of the probe 33-35" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351975&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351982&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351978&type=" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2.2　特异性检测MAO-A的荧光探针" } ], "level": "3", "id": "s2b2" } }, { "name": "p", "data": [ { "name": "text", "data": "MAO-A和MAO-B虽然都与神经退行性疾病、发育性残疾及严重智力障碍有关，但是它们的序列并不完全一致，在细胞及组织中的分布不同，底物及抑制剂不同。为了进一步明确MAO-A和MAO-B的功能差异及其在相关疾病中所起的作用，非常有必要开发特异性监测MAO-A或MAO-B的荧光探针。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "2016年，中科院化学所马会民课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "62", "type": "bibr", "rid": "R62", "data": [ { "name": "text", "data": "62" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "首次报道了特异性识别MAO-A的比率型荧光探针36a和36b，如" }, { "name": "xref", "data": { "text": "图15", "type": "fig", "rid": "F15", "data": [ { "name": "text", "data": "图15" } ] } }, { "name": "text", "data": "所示。该体系采用氨基丙基作为MAO-A的响应基团，具有比率型荧光变化的萘二甲酰亚胺作为荧光基团，探针36a和36b与MAO-A作用后可产生蓝色荧光到绿色荧光的比率变化，对MAO-B基本不响应。36a和36b对MAO-A的检测限分别为1.1 ng/mL和10 ng/mL。该课题组通过分子对接研究了探针36a对MAO-A及MAO-B的亲和力，结果表明探针36a与MAO-A对接打分值(-lg" }, { "name": "italic", "data": [ { "name": "text", "data": "K" } ] }, { "name": "sub", "data": [ { "name": "text", "data": "d" } ] }, { "name": "text", "data": ")比MAO-B高近一倍，说明探针36a与MAO-A的结合比MAO-B强，并且探针36a与MAO-A存在潜在的氢键作用。鉴于其对MAO-A具有更好的灵敏度，探针36a可用于实时检测HeLa细胞和NIH-3T3细胞中MAO-A的表达水平。实验结果表明，HeLa细胞中MAO-A的表达水平比NIH-3T3细胞中MAO-A表达水平高1.8倍，与商业化ELISA试剂盒所得结果一致。" } ] }, { "name": "fig", "data": { "id": "F15", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图15" } ], "title": [ { "name": "text", "data": "(a)探针36a和36b的结构;(b)探针36a和36b对MAOs响应后的荧光比率变化;(c)探针36a在Hela和NIH-3T3细胞中的荧光成像。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.15" } ], "title": [ { "name": "text", "data": "(a)Structures of the probe 36a and 36b. (b)Ratio changes of fluorescence intensity of probe 36a and 36b upon reaction with MAO-A and MAO-B. (c)Fluorescence images of probe 36a in Hela cells and NIH-3T3." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351986&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351994&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351990&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "2017年，该课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "63", "type": "bibr", "rid": "R63", "data": [ { "name": "text", "data": "63" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "根据MAO-A抑制剂氯吉兰的结构进一步设计合成了能够特异性检测MAO-A的荧光探针37~42。如" }, { "name": "xref", "data": { "text": "图16", "type": "fig", "rid": "F16", "data": [ { "name": "text", "data": "图16" } ] } }, { "name": "text", "data": "所示，探针39和40表现出对MAO-A的高特异性响应，对MAO-A和MAO-B的响应比分别为42和41倍。探针39可用于区分MAO-A高表达的SH-SY5Y细胞和MAO-B高表达的HepG2细胞。2021年，该课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "64", "type": "bibr", "rid": "R64", "data": [ { "name": "text", "data": "64" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "根据类似的思路开发了两种水溶性近红外荧光探针43和44，其发射达到了708 nm，可以特异性识别MAO-A。其中探针43检测限为4.5 ng/mL，对MAO-A的特异性是MAO-B的13倍。探针43已成功应用于细胞、斑马鱼和荷瘤小鼠中MAO-A荧光成像，在肿瘤MAO-A的活性研究中展示出广阔的应用前景。" } ] }, { "name": "fig", "data": { "id": "F16", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图16" } ], "title": [ { "name": "text", "data": "探针37~42的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.16" } ], "title": [ { "name": "text", "data": "Structures of the probe 37-42" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21351998&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352006&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352002&type=" } ] } }, { "name": "fig", "data": { "id": "F17", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图17" } ], "title": [ { "name": "text", "data": "探针43~44的结构及对MAO-A的响应机制" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.17" } ], "title": [ { "name": "text", "data": "Structures of the probe 43-44 and the response mechanism to MAO-A" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352010&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352018&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352014&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "随后，广西师范大学的覃江克和李俊课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "65", "type": "bibr", "rid": "R65", "data": [ { "name": "text", "data": "65" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "根据相似的设计思路，开发了特异性响应MAO-A的近红外荧光探针45~50。如" }, { "name": "xref", "data": { "text": "图18", "type": "fig", "rid": "F18", "data": [ { "name": "text", "data": "图18" } ] } }, { "name": "text", "data": "所示，这类探针结构中" }, { "name": "italic", "data": [ { "name": "text", "data": "R" } ] }, { "name": "text", "data": "基团与其对MAOs的选择性具有至关重要的作用，当" }, { "name": "italic", "data": [ { "name": "text", "data": "R" } ] }, { "name": "text", "data": "基团为Cl时，探针的靶向单元与MAO-A特异性抑制剂氯吉兰的结构非常类似，因此探针47对MAO-A具有特异性响应。探针46和48分别将" }, { "name": "italic", "data": [ { "name": "text", "data": "R" } ] }, { "name": "text", "data": "基团改为F和Br，结构仍与氯吉兰相近，因此探针46和48也表现出对MAO-A的特异性。而探针45的" }, { "name": "italic", "data": [ { "name": "text", "data": "R" } ] }, { "name": "text", "data": "基团为H，对两种MAOs均有响应。探针49和50的R基团为甲基和甲氧基，可能由于空间位阻过大，导致这两个探针对MAOs均不响应。探针47成功用于斑马鱼及荷瘤小鼠肿瘤部位MAO-A的实时荧光成像，将成为深入了解MAO-A生理功能的新工具。同年，该课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "66", "type": "bibr", "rid": "R66", "data": [ { "name": "text", "data": "66" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "又进一步发展了可靶向线粒体的MAO-A特异性近红外荧光探针51，如" }, { "name": "xref", "data": { "text": "图19(a)", "type": "fig", "rid": "F19", "data": [ { "name": "text", "data": "图19(a)" } ] } }, { "name": "text", "data": "所示。探针51除了具有对斑马鱼和荷瘤小鼠中MAO-A特异性实时成像能力外，还首次用于检测肝脏纤维化组织中MAO-A的活性，有望用作肝脏疾病的新型诊断工具。" } ] }, { "name": "fig", "data": { "id": "F18", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图18" } ], "title": [ { "name": "text", "data": "(a)探针45~50的结构和对MAO-A的响应过程;(b)探针45~50对MAOs响应的荧光强度变化; (c)探针47在斑马鱼中的荧光成像;(d)探针47在小鼠肿瘤中的荧光成像。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.18" } ], "title": [ { "name": "text", "data": "(a)Structures of the probe 45-50 and their response to MAO-A. (b)Ratio of fluorescence intensity of probe 45-50 to MAOs. (c)Fluorescence images of MAO-A with probe 47 in 3 day-old zebrafish larvae. (d)" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " fluorescence images of MAO-A activity in tumor-bearing nude mice by probe 47." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352022&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352030&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352026&type=" } ] } }, { "name": "fig", "data": { "id": "F19", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图19" } ], "title": [ { "name": "text", "data": "(a)探针51的结构;(b)探针52的结构及响应机制。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.19" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 51. (b)Structure of the probe 52 and the response mechanism." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352031&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352042&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352037&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "2020年，南京工业大学的李林" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "67", "type": "bibr", "rid": "R67", "data": [ { "name": "text", "data": "67" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "联合新加坡国立大学姚少钦和西北工业大学的黄维课题组设计开发了用于MAO-A特异性检测的双光子荧光探针52，如" }, { "name": "xref", "data": { "text": "图19(b)", "type": "fig", "rid": "F19", "data": [ { "name": "text", "data": "图19(b)" } ] } }, { "name": "text", "data": "所示。探针52的双光子性质使其可用于多种生物样本中MAO-A的特异性荧光检测，如MAO-A高表达的SY-SY5Y细胞、荷瘤小鼠及人胶质瘤组织等。" } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2.3　特异性检测MAO-B的荧光探针" } ], "level": "3", "id": "s2b3" } }, { "name": "p", "data": [ { "name": "text", "data": "MAO-B是MAOs的另一个亚型，通常用作药物开发的靶标。2012年，朱勍课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "68", "type": "bibr", "rid": "R68", "data": [ { "name": "text", "data": "68" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "利用MAO-B特异性的α-C—O键的氧化断裂策略设计合成了一系列MAOs荧光探针53a~53c，如" }, { "name": "xref", "data": { "text": "图20", "type": "fig", "rid": "F20", "data": [ { "name": "text", "data": "图20" } ] } }, { "name": "text", "data": "所示。其中探针53a对MAO-B的响应比MAO-A高出22倍。随后，该课题组利用相同的策略设计合成" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "69", "type": "bibr", "rid": "R69", "data": [ { "name": "text", "data": "69" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "了一系列MAO-B特异性的荧光探针54a~54d，如" }, { "name": "xref", "data": { "text": "图21(a)", "type": "fig", "rid": "F21", "data": [ { "name": "text", "data": "图21(a)" } ] } }, { "name": "text", "data": "所示，并将其用于活细胞中MAO-B的实时荧光成像。" } ] }, { "name": "fig", "data": { "id": "F20", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图20" } ], "title": [ { "name": "text", "data": "(a)探针53a~53c的结构;(b)探针53a~53c对MAO-B的选择性响应;探针53a与人MAO-A(c)和MAO-B(d)活性位点的结合方式。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.20" } ], "title": [ { "name": "text", "data": "(a)Structures of the probe 53a-53c. (b)Selective response of probes 53a-53c to MAO-B. Combination mode of probe 53a and active site of human MAO-A(c) and MAO-B(d)." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352045&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352058&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352052&type=" } ] } }, { "name": "fig", "data": { "id": "F21", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图21" } ], "title": [ { "name": "text", "data": "(a)探针54a~54d的结构;(b)探针55对MAO-B的响应机制。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.21" } ], "title": [ { "name": "text", "data": "(a)Structures of the probe 54a-54d. (b)Response mechanism of probe 55 to MAO-B." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352063&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352072&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352068&type=" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "新加坡国立大学姚少钦课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "70", "type": "bibr", "rid": "R70", "data": [ { "name": "text", "data": "70" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "报道了第一个可用于特异性检测MAO-B的双光子荧光探针55，如" }, { "name": "xref", "data": { "text": "图21(b)", "type": "fig", "rid": "F21", "data": [ { "name": "text", "data": "图21(b)" } ] } }, { "name": "text", "data": "所示。探针55是基于MAO-A和MAO-B的活性部位的差异及分子对接结果筛选获得的。MAO-A的活性部位包含一个单独的体积为0.55 nm" }, { "name": "sup", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": "的疏水空腔，而MAO-B的活性部位更长更狭窄，包含一个入口空腔和一个疏水的底物空腔，体积分别为0.290 nm" }, { "name": "sup", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": "和0.490 nm" }, { "name": "sup", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": "。分子对接研究结果表明，探针55可紧密贴合MAO-B的底物空腔，其一级胺部分面向MAO-B中的辅酶FAD，因此探针55可对生物样本中内源性MAO-B表现出高灵敏度、高特异性，对MAO-B具有实时成像能力，并且还可用于检测帕金森病人样本中的MAO-B。实验结果表明，帕金森病人淋巴细胞中MAO-B的表达明显升高。探针55的开发对帕金森综合症的研究具有重要意义。该研究结果为小分子成像技术在生物水平上探索MAO-B的化学和生物学结构及功能提供了新的起点，也为基础研究、诊断和药物发现提供了有效的工具。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "2018年，曲阜师范大学的陈令新课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "71", "type": "bibr", "rid": "R71", "data": [ { "name": "text", "data": "71" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "开发了近红外MAO-B荧光探针56，如" }, { "name": "xref", "data": { "text": "图22", "type": "fig", "rid": "F22", "data": [ { "name": "text", "data": "图22" } ] } }, { "name": "text", "data": "所示。他们认为该探针对MAO-B的高特异性可能来自于探针分子的化学结构对酶的空间位阻效应。56可通过比率型近红外荧光的变化特异性检测双氧水诱导的小鼠老龄化模型中的MAO-B，结果表明，小鼠模型中MAO-B的水平随小鼠老龄化程度的增加而显著升高。2019年，四川大学余孝其及李坤课题组" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "72", "type": "bibr", "rid": "R72", "data": [ { "name": "text", "data": "72" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "利用MAO-B催化的级联反应设计合成了对MAO-B特异性响应的荧光探针57和58，如" }, { "name": "xref", "data": { "text": "图23", "type": "fig", "rid": "F23", "data": [ { "name": "text", "data": "图23" } ] } }, { "name": "text", "data": "所示。这两个探针对MAO-B的检测限分别为0.6 ng/mL和0.2 ng/mL，并能够用于人星形胶质肿瘤细胞U87中MAO-B的荧光成像。" } ] }, { "name": "fig", "data": { "id": "F22", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图22" } ], "title": [ { "name": "text", "data": "(a)探针56的化学结构;(b)用探针56评价抑制剂小鼠经PA和SE处理后的MAO-B水平;(c)从图(b)中分离得到的新鲜小鼠黑质致密部脑组织切片荧光成像图。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.22" } ], "title": [ { "name": "text", "data": "(a)Structure of the probe 56. (b)Evaluation of the therapeutic effect of PA and SE " }, { "name": "italic", "data": [ { "name": "text", "data": "in vivo" } ] }, { "name": "text", "data": " using 56. (c)Fluorescence imaging for slices of fresh mice SNpc(substantia nigra pars compacta) isolated from panel(b)." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352076&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352085&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352080&type=" } ] } }, { "name": "fig", "data": { "id": "F23", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图23" } ], "title": [ { "name": "text", "data": "探针57和58的结构" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.23" } ], "title": [ { "name": "text", "data": "Structures of the probe 57 and 58" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352090&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352099&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21352094&type=" } ] } } ] } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3　结论与展望" } ], "level": "1", "id": "s3" } }, { "name": "p", "data": [ { "name": "text", "data": "本文综述了近年来发展起来的检测MAOs的结合型和反应型荧光探针。有关MAOs荧光探针的研究虽已取得了长足进步，但仍有许多问题有待于科学家们解决。(1)能够准确区分的MAO-A或MAO-B的荧光探针仍少之又少;(2)具有近红外发射波长对MAO-A或MAO-B高灵敏度、高选择性的荧光探针的开发仍极具挑战性;(3)考虑到AIE探针聚集后仍保持高发光强度、良好的光稳定性及较大的Stokes位移等独特的光物理性质，开发具有AIE特性的MAOs荧光探针具有广阔的发展空间;(4)具有高灵敏度的MAOs诊疗一体化荧光探针的开发仍然十分有限;(5)MAOs荧光探针在临床应用中的开发尚处于发展初期。尽管如此，随着理论化学的不断发展、更加准确的计算方法的提出，我们坚信，在国内外理论与实验科学家的共同努力下，有关MAOs荧光探针的开发有望更好地阐明MAOs在健康和疾病中的复杂作用，最终走向临床应用，从而造福人类。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "本文专家审稿意见及作者回复内容的下载地址:http://cjl.lightpublishing.cn/thesisDetails#10.37188/CJL.20210086" } ] } ] } ], "footnote": [], "reflist": { "title": [ { "name": "text", "data": "参考文献:" } ], "data": [ { "id": "R1", "label": "[1]", "citation": [ { "lang": "en", "text": [ { "name": "text", "data": "BERRY M D" }, { "name": "text", "data": ", " }, { "name": "text", "data": "JUORIO A V" }, { "name": "text", "data": ", " }, { "name": "text", "data": "PATERSON I A" }, { "name": "text", "data": ". 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