A Ratiometric Fluorescent Probe for Monitoring Leucine Aminopeptidase in Living Cells and Zebrafish Model
Leucine aminopeptidase (LAP) is an important cancer-related biomarker, which shows significant overexpression in malignant tumor cells like liver cancer. Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work,...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2017-11, Vol.89 (21), p.11576-11582 |
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| creator | Zhou, Zhe Wang, Feiyi Yang, Guichun Lu, Cuifen Nie, Junqi Chen, Zuxing Ren, Jun Sun, Qi Zhao, Chunchang Zhu, Wei-Hong |
| description | Leucine aminopeptidase (LAP) is an important cancer-related biomarker, which shows significant overexpression in malignant tumor cells like liver cancer. Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work, we report a novel BODIPY-based fluorescent probe (BODIPY-C-Leu) capable of monitoring LAP in vitro and in vivo in both ratiometric and turn-on model. BODIPY-C-Leu contains an asymmetrical BODIPY dye for fluorescent signaling and a dipeptide (Cys-Leu) as the triggered moiety. Activation occurs by cleavage of the amide bond in dipeptides and subsequently an intramolecular S → N conversion to convert sulfur-substituted BODIPY to amino-substituted BODIPY, resulting in a dramatic fluorescence variation to realize the detection of LAP. Furthermore, we have successfully employed BODIPY-C-Leu to monitor LAP activity in different cancer cells, indicating that HeLa cells have a higher level of LAP activity than A549 cells. Importantly, we demonstrated the capability of the probe for real-time monitoring the drug-induced LAP level changes in zebrafish. |
| doi_str_mv | 10.1021/acs.analchem.7b02910 |
| format | Article |
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Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work, we report a novel BODIPY-based fluorescent probe (BODIPY-C-Leu) capable of monitoring LAP in vitro and in vivo in both ratiometric and turn-on model. BODIPY-C-Leu contains an asymmetrical BODIPY dye for fluorescent signaling and a dipeptide (Cys-Leu) as the triggered moiety. Activation occurs by cleavage of the amide bond in dipeptides and subsequently an intramolecular S → N conversion to convert sulfur-substituted BODIPY to amino-substituted BODIPY, resulting in a dramatic fluorescence variation to realize the detection of LAP. Furthermore, we have successfully employed BODIPY-C-Leu to monitor LAP activity in different cancer cells, indicating that HeLa cells have a higher level of LAP activity than A549 cells. Importantly, we demonstrated the capability of the probe for real-time monitoring the drug-induced LAP level changes in zebrafish.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.7b02910</identifier><identifier>PMID: 28992691</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>A549 Cells ; Aminopeptidase ; Analytical chemistry ; Animals ; Biomarkers ; Boron Compounds - chemistry ; Cancer ; Cell Survival ; Chemistry ; Enzyme Assays - methods ; Fluorescence ; Fluorescent Dyes - chemistry ; HeLa Cells ; Hepatocytes ; Humans ; Kinetics ; Leucine ; Leucine - chemistry ; Leucyl Aminopeptidase - chemistry ; Leucyl Aminopeptidase - metabolism ; Liver ; Liver cancer ; Monitoring ; Optical Imaging ; Peptides ; Signal-To-Noise Ratio ; Signaling ; Substitutes ; Sulfur ; Tumor cells ; Zebrafish</subject><ispartof>Analytical chemistry (Washington), 2017-11, Vol.89 (21), p.11576-11582</ispartof><rights>Copyright © 2017 American Chemical Society</rights><rights>Copyright American Chemical Society Nov 7, 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a442t-eca4174107911fe7d8a45dfba015bae120ef98d1081b3bfdcd0e33c44772eecb3</citedby><cites>FETCH-LOGICAL-a442t-eca4174107911fe7d8a45dfba015bae120ef98d1081b3bfdcd0e33c44772eecb3</cites><orcidid>0000-0003-2936-5276 ; 0000-0001-9103-166X ; 0000-0003-2952-7036</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.7b02910$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.7b02910$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28992691$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Zhe</creatorcontrib><creatorcontrib>Wang, Feiyi</creatorcontrib><creatorcontrib>Yang, Guichun</creatorcontrib><creatorcontrib>Lu, Cuifen</creatorcontrib><creatorcontrib>Nie, Junqi</creatorcontrib><creatorcontrib>Chen, Zuxing</creatorcontrib><creatorcontrib>Ren, Jun</creatorcontrib><creatorcontrib>Sun, Qi</creatorcontrib><creatorcontrib>Zhao, Chunchang</creatorcontrib><creatorcontrib>Zhu, Wei-Hong</creatorcontrib><title>A Ratiometric Fluorescent Probe for Monitoring Leucine Aminopeptidase in Living Cells and Zebrafish Model</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Leucine aminopeptidase (LAP) is an important cancer-related biomarker, which shows significant overexpression in malignant tumor cells like liver cancer. Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work, we report a novel BODIPY-based fluorescent probe (BODIPY-C-Leu) capable of monitoring LAP in vitro and in vivo in both ratiometric and turn-on model. BODIPY-C-Leu contains an asymmetrical BODIPY dye for fluorescent signaling and a dipeptide (Cys-Leu) as the triggered moiety. Activation occurs by cleavage of the amide bond in dipeptides and subsequently an intramolecular S → N conversion to convert sulfur-substituted BODIPY to amino-substituted BODIPY, resulting in a dramatic fluorescence variation to realize the detection of LAP. Furthermore, we have successfully employed BODIPY-C-Leu to monitor LAP activity in different cancer cells, indicating that HeLa cells have a higher level of LAP activity than A549 cells. Importantly, we demonstrated the capability of the probe for real-time monitoring the drug-induced LAP level changes in zebrafish.</description><subject>A549 Cells</subject><subject>Aminopeptidase</subject><subject>Analytical chemistry</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Boron Compounds - chemistry</subject><subject>Cancer</subject><subject>Cell Survival</subject><subject>Chemistry</subject><subject>Enzyme Assays - methods</subject><subject>Fluorescence</subject><subject>Fluorescent Dyes - chemistry</subject><subject>HeLa Cells</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Leucine</subject><subject>Leucine - chemistry</subject><subject>Leucyl Aminopeptidase - chemistry</subject><subject>Leucyl Aminopeptidase - metabolism</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Monitoring</subject><subject>Optical Imaging</subject><subject>Peptides</subject><subject>Signal-To-Noise Ratio</subject><subject>Signaling</subject><subject>Substitutes</subject><subject>Sulfur</subject><subject>Tumor cells</subject><subject>Zebrafish</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2LFDEURYMoTjv6D0QCbtxU-14q3aksm8ZRoUUR3bgp8vHKyVCVtEmV4L83TfcouHCVzbn3kXsYe46wRhD42riyNtGM7pamtbIgNMIDtsKNgGbbdeIhWwFA2wgFcMWelHIHgAi4fcyuRKe12GpcsbDjn80c0kRzDo7fjEvKVBzFmX_KyRIfUuYfUgxzyiF-5wdaXIjEd1OI6UjHOXhTiIfID-HnCdjTOBZuouffyGYzhHJb857Gp-zRYMZCzy7vNft68-bL_l1z-Pj2_X53aIyUYm7IGYlKIiiNOJDynZEbP1gDuLGGUAANuvMIHdrWDt55oLZ1UioliJxtr9mrc-8xpx8LlbmfQv3QOJpIaSk9aqm3WiilK_ryH_QuLblueqK6Dcq2Dl0peaZcTqVkGvpjDpPJv3qE_qSiryr6exX9RUWNvbiUL3Yi_yd0v30F4Ayc4n8P_6_zN9CXmQg</recordid><startdate>20171107</startdate><enddate>20171107</enddate><creator>Zhou, Zhe</creator><creator>Wang, Feiyi</creator><creator>Yang, Guichun</creator><creator>Lu, Cuifen</creator><creator>Nie, Junqi</creator><creator>Chen, Zuxing</creator><creator>Ren, Jun</creator><creator>Sun, Qi</creator><creator>Zhao, Chunchang</creator><creator>Zhu, Wei-Hong</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2936-5276</orcidid><orcidid>https://orcid.org/0000-0001-9103-166X</orcidid><orcidid>https://orcid.org/0000-0003-2952-7036</orcidid></search><sort><creationdate>20171107</creationdate><title>A Ratiometric Fluorescent Probe for Monitoring Leucine Aminopeptidase in Living Cells and Zebrafish Model</title><author>Zhou, Zhe ; 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Chem</addtitle><date>2017-11-07</date><risdate>2017</risdate><volume>89</volume><issue>21</issue><spage>11576</spage><epage>11582</epage><pages>11576-11582</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>Leucine aminopeptidase (LAP) is an important cancer-related biomarker, which shows significant overexpression in malignant tumor cells like liver cancer. Developing an effective method to monitor LAP in tumor cells holds great potential for cancer diagnosis, treatment, and management. In this work, we report a novel BODIPY-based fluorescent probe (BODIPY-C-Leu) capable of monitoring LAP in vitro and in vivo in both ratiometric and turn-on model. BODIPY-C-Leu contains an asymmetrical BODIPY dye for fluorescent signaling and a dipeptide (Cys-Leu) as the triggered moiety. Activation occurs by cleavage of the amide bond in dipeptides and subsequently an intramolecular S → N conversion to convert sulfur-substituted BODIPY to amino-substituted BODIPY, resulting in a dramatic fluorescence variation to realize the detection of LAP. Furthermore, we have successfully employed BODIPY-C-Leu to monitor LAP activity in different cancer cells, indicating that HeLa cells have a higher level of LAP activity than A549 cells. Importantly, we demonstrated the capability of the probe for real-time monitoring the drug-induced LAP level changes in zebrafish.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>28992691</pmid><doi>10.1021/acs.analchem.7b02910</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-2936-5276</orcidid><orcidid>https://orcid.org/0000-0001-9103-166X</orcidid><orcidid>https://orcid.org/0000-0003-2952-7036</orcidid></addata></record> |
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| subjects | A549 Cells Aminopeptidase Analytical chemistry Animals Biomarkers Boron Compounds - chemistry Cancer Cell Survival Chemistry Enzyme Assays - methods Fluorescence Fluorescent Dyes - chemistry HeLa Cells Hepatocytes Humans Kinetics Leucine Leucine - chemistry Leucyl Aminopeptidase - chemistry Leucyl Aminopeptidase - metabolism Liver Liver cancer Monitoring Optical Imaging Peptides Signal-To-Noise Ratio Signaling Substitutes Sulfur Tumor cells Zebrafish |
| title | A Ratiometric Fluorescent Probe for Monitoring Leucine Aminopeptidase in Living Cells and Zebrafish Model |
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