{"title":"利用新型荧光探针以免洗方式同时观察银屑病小鼠模型中的脂滴并追踪内源性次氯酸。","authors":"Xuan Zhao, Xiaoxue Hu, Longxuan Li, Yuanping Liu, Boshuang Song, Yuzhi Li, Zhixing Cao, Houcheng Zhou, Cheng Peng, Yun Deng, Yuyu Fang","doi":"10.1016/j.bioorg.2024.107967","DOIUrl":null,"url":null,"abstract":"<p><p>Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl<sup>-</sup>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Endogenous HOCl has recently been studied as a potential biomarker of psoriasis underlying the necessity for the development of efficient analytical tools for its detection and real time monitoring. Herein, we designed a novel highly sensitive and selective coumarin-based fluorescent probe for HOCl detection, named CN<sub>2</sub>-CF<sub>3</sub>-S. The probe itself featured negligible fluorescence because of the heavy atom effect of the thiocarbonyl group. However, upon responding to HOCl a conversion to sulfur-free derivative CN<sub>2</sub>-CF<sub>3</sub>-O occurs, resulting in a dramatical fluorescent enhancement setting the detection limit for HOCl of 3.2 nM. The HOCl-recognition mechanism could be ascribed to the HOCl-triggered oxidative desulfurization process that agrees with liquid chromatography-mass spectrometry (LC-MS) analysis and density functional theory (DFT) computations. The probe's design incorporated a synergistic combination of two structural features for efficient lipid droplets (LDs)-targeting imaging. An efficient push-pull system reinforced by the presence of two strongly electron-donating dimethylamino groups equipped CN<sub>2</sub>-CF<sub>3</sub>-O with pronounced solvatochromism realized through the enhanced blue-shifted emission in non-polar media. Meanwhile, the presence of trifluormethylphenyl moiety at the acceptor side led to an increased lipophilicity. The CN<sub>2</sub>-CF<sub>3</sub>-S probe has been successfully utilized to track the endogenous HOCl in cells and on skin of the psoriatic mice in a wash-free manner. As a result, we have demonstrated that the concentration of HOCl in skin might correlate positively with the degree of inflammation in psoriasis. Thus, CN<sub>2</sub>-CF<sub>3</sub>-S constitutes the first example of LDs-imaging fluorescent probe for detecting the psoriasis-linked HOCl, offering a convenient tool for further in-depth investigation of psoriasis pathophysiology.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107967"},"PeriodicalIF":4.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion.\",\"authors\":\"Xuan Zhao, Xiaoxue Hu, Longxuan Li, Yuanping Liu, Boshuang Song, Yuzhi Li, Zhixing Cao, Houcheng Zhou, Cheng Peng, Yun Deng, Yuyu Fang\",\"doi\":\"10.1016/j.bioorg.2024.107967\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl<sup>-</sup>) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Endogenous HOCl has recently been studied as a potential biomarker of psoriasis underlying the necessity for the development of efficient analytical tools for its detection and real time monitoring. Herein, we designed a novel highly sensitive and selective coumarin-based fluorescent probe for HOCl detection, named CN<sub>2</sub>-CF<sub>3</sub>-S. The probe itself featured negligible fluorescence because of the heavy atom effect of the thiocarbonyl group. However, upon responding to HOCl a conversion to sulfur-free derivative CN<sub>2</sub>-CF<sub>3</sub>-O occurs, resulting in a dramatical fluorescent enhancement setting the detection limit for HOCl of 3.2 nM. The HOCl-recognition mechanism could be ascribed to the HOCl-triggered oxidative desulfurization process that agrees with liquid chromatography-mass spectrometry (LC-MS) analysis and density functional theory (DFT) computations. The probe's design incorporated a synergistic combination of two structural features for efficient lipid droplets (LDs)-targeting imaging. An efficient push-pull system reinforced by the presence of two strongly electron-donating dimethylamino groups equipped CN<sub>2</sub>-CF<sub>3</sub>-O with pronounced solvatochromism realized through the enhanced blue-shifted emission in non-polar media. Meanwhile, the presence of trifluormethylphenyl moiety at the acceptor side led to an increased lipophilicity. The CN<sub>2</sub>-CF<sub>3</sub>-S probe has been successfully utilized to track the endogenous HOCl in cells and on skin of the psoriatic mice in a wash-free manner. As a result, we have demonstrated that the concentration of HOCl in skin might correlate positively with the degree of inflammation in psoriasis. Thus, CN<sub>2</sub>-CF<sub>3</sub>-S constitutes the first example of LDs-imaging fluorescent probe for detecting the psoriasis-linked HOCl, offering a convenient tool for further in-depth investigation of psoriasis pathophysiology.</p>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":\"153 \",\"pages\":\"107967\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1016/j.bioorg.2024.107967\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.bioorg.2024.107967","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion.
Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl-) and hydrogen peroxide (H2O2). Endogenous HOCl has recently been studied as a potential biomarker of psoriasis underlying the necessity for the development of efficient analytical tools for its detection and real time monitoring. Herein, we designed a novel highly sensitive and selective coumarin-based fluorescent probe for HOCl detection, named CN2-CF3-S. The probe itself featured negligible fluorescence because of the heavy atom effect of the thiocarbonyl group. However, upon responding to HOCl a conversion to sulfur-free derivative CN2-CF3-O occurs, resulting in a dramatical fluorescent enhancement setting the detection limit for HOCl of 3.2 nM. The HOCl-recognition mechanism could be ascribed to the HOCl-triggered oxidative desulfurization process that agrees with liquid chromatography-mass spectrometry (LC-MS) analysis and density functional theory (DFT) computations. The probe's design incorporated a synergistic combination of two structural features for efficient lipid droplets (LDs)-targeting imaging. An efficient push-pull system reinforced by the presence of two strongly electron-donating dimethylamino groups equipped CN2-CF3-O with pronounced solvatochromism realized through the enhanced blue-shifted emission in non-polar media. Meanwhile, the presence of trifluormethylphenyl moiety at the acceptor side led to an increased lipophilicity. The CN2-CF3-S probe has been successfully utilized to track the endogenous HOCl in cells and on skin of the psoriatic mice in a wash-free manner. As a result, we have demonstrated that the concentration of HOCl in skin might correlate positively with the degree of inflammation in psoriasis. Thus, CN2-CF3-S constitutes the first example of LDs-imaging fluorescent probe for detecting the psoriasis-linked HOCl, offering a convenient tool for further in-depth investigation of psoriasis pathophysiology.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.