Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins
Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity....
Gespeichert in:
| Veröffentlicht in: | Doklady. Biochemistry and biophysics 2019-11, Vol.489 (1), p.370-372 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 372 |
|---|---|
| container_issue | 1 |
| container_start_page | 370 |
| container_title | Doklady. Biochemistry and biophysics |
| container_volume | 489 |
| creator | Khodarovich, Yu. M. Konovalova, E. V. Schulga, A. A. Deyev, S. M. Petrov, R. V. |
| description | Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity. In our work on human cell line, we have shown that the removal of the DARPin-PE40 translocation toxin domain leads to a decrease in hepatotoxicity. The same effect is also observed when inactivation of the furin cleavage site in the DARPin-PE40 molecule was done. Simultaneous removal of both the translocation domain and the furin cleavage site showed the best results. This toxin modification can be used to create more selective anti-cancer toxins. |
| doi_str_mv | 10.1134/S1607672919060048 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2371172084</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2371172084</sourcerecordid><originalsourceid>FETCH-LOGICAL-c324t-744a427da6599ed0d998f12dd53d18ad4bd096e8d472375b38a30347d3cb20143</originalsourceid><addsrcrecordid>eNp1kM1OAjEUhRujEUQfwI1p4nq0f0xnlgRETEhMANeTMr3gkJkpth0iL-BzW37EhXF1e3u-c25yELql5IFSLh6nNCYyliylKYkJEckZaoevJOIkpef7t4x2egtdObcihBHGu5eoxRnlwcHa6GsCldmoEpsF9u-AZ1bVrjS58oWp8cBUqqixqvVeHDY2bP0S1EYtAU8LD3gAuQXlwO2JCZTBuQE8grXyxpvPIi_89pSu7BI8aNyrfeGbylg8C0jtrtHFQpUObo6zg96GT7P-KBq_Pr_0e-Mo50z4SAqhBJNaxd00BU10miYLyrTuck0TpcVckzSGRAvJuOzOeaI44UJqns8ZoYJ30P0hd23NRwPOZyvT2DqczIKBUslIsqPogcqtcc7CIlvbolJ2m1GS7ZrP_jQfPHfH5GZegT45fqoOADsALkj1Euzv6f9TvwHmeI2t</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2371172084</pqid></control><display><type>article</type><title>Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Khodarovich, Yu. M. ; Konovalova, E. V. ; Schulga, A. A. ; Deyev, S. M. ; Petrov, R. V.</creator><creatorcontrib>Khodarovich, Yu. M. ; Konovalova, E. V. ; Schulga, A. A. ; Deyev, S. M. ; Petrov, R. V.</creatorcontrib><description>Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity. In our work on human cell line, we have shown that the removal of the DARPin-PE40 translocation toxin domain leads to a decrease in hepatotoxicity. The same effect is also observed when inactivation of the furin cleavage site in the DARPin-PE40 molecule was done. Simultaneous removal of both the translocation domain and the furin cleavage site showed the best results. This toxin modification can be used to create more selective anti-cancer toxins.</description><identifier>ISSN: 1607-6729</identifier><identifier>EISSN: 1608-3091</identifier><identifier>DOI: 10.1134/S1607672919060048</identifier><identifier>PMID: 32130602</identifier><language>eng</language><publisher>Moscow: Pleiades Publishing</publisher><subject>Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Antitumor agents ; Binding Sites ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biophysics ; Cancer ; Cell Line, Tumor ; Furin ; Furin - chemistry ; Furin - metabolism ; Hep G2 Cells ; Hepatotoxicity ; Humans ; Life Sciences ; Liver - drug effects ; Molecular Biology ; Molecular Targeted Therapy ; Protein Domains ; Protein Transport - drug effects ; Toxins</subject><ispartof>Doklady. Biochemistry and biophysics, 2019-11, Vol.489 (1), p.370-372</ispartof><rights>Pleiades Publishing, Ltd. 2019</rights><rights>2019© Pleiades Publishing, Ltd. 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c324t-744a427da6599ed0d998f12dd53d18ad4bd096e8d472375b38a30347d3cb20143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1134/S1607672919060048$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1134/S1607672919060048$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32130602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khodarovich, Yu. M.</creatorcontrib><creatorcontrib>Konovalova, E. V.</creatorcontrib><creatorcontrib>Schulga, A. A.</creatorcontrib><creatorcontrib>Deyev, S. M.</creatorcontrib><creatorcontrib>Petrov, R. V.</creatorcontrib><title>Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins</title><title>Doklady. Biochemistry and biophysics</title><addtitle>Dokl Biochem Biophys</addtitle><addtitle>Dokl Biochem Biophys</addtitle><description>Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity. In our work on human cell line, we have shown that the removal of the DARPin-PE40 translocation toxin domain leads to a decrease in hepatotoxicity. The same effect is also observed when inactivation of the furin cleavage site in the DARPin-PE40 molecule was done. Simultaneous removal of both the translocation domain and the furin cleavage site showed the best results. This toxin modification can be used to create more selective anti-cancer toxins.</description><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antitumor agents</subject><subject>Binding Sites</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Furin</subject><subject>Furin - chemistry</subject><subject>Furin - metabolism</subject><subject>Hep G2 Cells</subject><subject>Hepatotoxicity</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Liver - drug effects</subject><subject>Molecular Biology</subject><subject>Molecular Targeted Therapy</subject><subject>Protein Domains</subject><subject>Protein Transport - drug effects</subject><subject>Toxins</subject><issn>1607-6729</issn><issn>1608-3091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1OAjEUhRujEUQfwI1p4nq0f0xnlgRETEhMANeTMr3gkJkpth0iL-BzW37EhXF1e3u-c25yELql5IFSLh6nNCYyliylKYkJEckZaoevJOIkpef7t4x2egtdObcihBHGu5eoxRnlwcHa6GsCldmoEpsF9u-AZ1bVrjS58oWp8cBUqqixqvVeHDY2bP0S1EYtAU8LD3gAuQXlwO2JCZTBuQE8grXyxpvPIi_89pSu7BI8aNyrfeGbylg8C0jtrtHFQpUObo6zg96GT7P-KBq_Pr_0e-Mo50z4SAqhBJNaxd00BU10miYLyrTuck0TpcVckzSGRAvJuOzOeaI44UJqns8ZoYJ30P0hd23NRwPOZyvT2DqczIKBUslIsqPogcqtcc7CIlvbolJ2m1GS7ZrP_jQfPHfH5GZegT45fqoOADsALkj1Euzv6f9TvwHmeI2t</recordid><startdate>20191101</startdate><enddate>20191101</enddate><creator>Khodarovich, Yu. M.</creator><creator>Konovalova, E. V.</creator><creator>Schulga, A. A.</creator><creator>Deyev, S. M.</creator><creator>Petrov, R. V.</creator><general>Pleiades Publishing</general><general>Springer Nature B.V</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope></search><sort><creationdate>20191101</creationdate><title>Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins</title><author>Khodarovich, Yu. M. ; Konovalova, E. V. ; Schulga, A. A. ; Deyev, S. M. ; Petrov, R. V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c324t-744a427da6599ed0d998f12dd53d18ad4bd096e8d472375b38a30347d3cb20143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antitumor agents</topic><topic>Binding Sites</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysics</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Furin</topic><topic>Furin - chemistry</topic><topic>Furin - metabolism</topic><topic>Hep G2 Cells</topic><topic>Hepatotoxicity</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Liver - drug effects</topic><topic>Molecular Biology</topic><topic>Molecular Targeted Therapy</topic><topic>Protein Domains</topic><topic>Protein Transport - drug effects</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khodarovich, Yu. M.</creatorcontrib><creatorcontrib>Konovalova, E. V.</creatorcontrib><creatorcontrib>Schulga, A. A.</creatorcontrib><creatorcontrib>Deyev, S. M.</creatorcontrib><creatorcontrib>Petrov, R. V.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Doklady. Biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khodarovich, Yu. M.</au><au>Konovalova, E. V.</au><au>Schulga, A. A.</au><au>Deyev, S. M.</au><au>Petrov, R. V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins</atitle><jtitle>Doklady. Biochemistry and biophysics</jtitle><stitle>Dokl Biochem Biophys</stitle><addtitle>Dokl Biochem Biophys</addtitle><date>2019-11-01</date><risdate>2019</risdate><volume>489</volume><issue>1</issue><spage>370</spage><epage>372</epage><pages>370-372</pages><issn>1607-6729</issn><eissn>1608-3091</eissn><abstract>Targeted toxins are promising anticancer agents that allow selectively destroying cancer cells due to the increased content of onco-specific markers on their surface. The use of such anti-cancer toxins in medicine is mainly hampered by their high non-specific toxicity, in particular, hepatotoxicity. In our work on human cell line, we have shown that the removal of the DARPin-PE40 translocation toxin domain leads to a decrease in hepatotoxicity. The same effect is also observed when inactivation of the furin cleavage site in the DARPin-PE40 molecule was done. Simultaneous removal of both the translocation domain and the furin cleavage site showed the best results. This toxin modification can be used to create more selective anti-cancer toxins.</abstract><cop>Moscow</cop><pub>Pleiades Publishing</pub><pmid>32130602</pmid><doi>10.1134/S1607672919060048</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1607-6729 |
| ispartof | Doklady. Biochemistry and biophysics, 2019-11, Vol.489 (1), p.370-372 |
| issn | 1607-6729 1608-3091 |
| language | eng |
| recordid | cdi_proquest_journals_2371172084 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use Antitumor agents Binding Sites Biochemistry Biological and Medical Physics Biomedical and Life Sciences Biophysics Cancer Cell Line, Tumor Furin Furin - chemistry Furin - metabolism Hep G2 Cells Hepatotoxicity Humans Life Sciences Liver - drug effects Molecular Biology Molecular Targeted Therapy Protein Domains Protein Transport - drug effects Toxins |
| title | Removal of the Translocation Domain and the Furin Cleavage Site Decreases the Relative Hepatotoxicity of the Targeted Antitumor Toxins |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T11%3A06%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Removal%20of%20the%20Translocation%20Domain%20and%20the%20Furin%20Cleavage%20Site%20Decreases%20the%20Relative%20Hepatotoxicity%20of%20the%20Targeted%20Antitumor%20Toxins&rft.jtitle=Doklady.%20Biochemistry%20and%20biophysics&rft.au=Khodarovich,%20Yu.%20M.&rft.date=2019-11-01&rft.volume=489&rft.issue=1&rft.spage=370&rft.epage=372&rft.pages=370-372&rft.issn=1607-6729&rft.eissn=1608-3091&rft_id=info:doi/10.1134/S1607672919060048&rft_dat=%3Cproquest_cross%3E2371172084%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2371172084&rft_id=info:pmid/32130602&rfr_iscdi=true |