A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines
L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane...
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Veröffentlicht in: | Journal of biochemical and molecular toxicology 2004, Vol.18 (4), p.204-220 |
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description | L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:204–220, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20025 |
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Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:204–220, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20025</description><identifier>ISSN: 1095-6670</identifier><identifier>EISSN: 1099-0461</identifier><identifier>DOI: 10.1002/jbt.20025</identifier><identifier>PMID: 15452885</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Amino Acid Sequence ; Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Cardiotoxin ; Caspases - drug effects ; Cell Line ; Cell Line, Tumor ; Cell Survival - drug effects ; Circular Dichroism ; Cobra Cardiotoxin Proteins - chemical synthesis ; Cobra Cardiotoxin Proteins - pharmacology ; Cyclic ; Humans ; L1AD3 ; Leukemia - pathology ; Leukemic ; Leukocytes ; Leukocytes - drug effects ; Models, Molecular ; Naja naja Atra ; Peptide ; Protein Conformation ; Protein Structure, Tertiary ; Rats ; Structure-Activity Relationship ; T-cell ; T-Lymphocytes - drug effects</subject><ispartof>Journal of biochemical and molecular toxicology, 2004, Vol.18 (4), p.204-220</ispartof><rights>Copyright © 2004 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3225-9d591071c9cd6953ba15208fa959e11a20c83402b7d50ba0b7a6761a934406de3</citedby><cites>FETCH-LOGICAL-c3225-9d591071c9cd6953ba15208fa959e11a20c83402b7d50ba0b7a6761a934406de3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbt.20025$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbt.20025$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,4024,27923,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15452885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smith, Charles A.</creatorcontrib><creatorcontrib>Hinman, Channing L.</creatorcontrib><title>A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines</title><title>Journal of biochemical and molecular toxicology</title><addtitle>J. Biochem. Mol. Toxicol</addtitle><description>L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:204–220, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20025</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Cardiotoxin</subject><subject>Caspases - drug effects</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Circular Dichroism</subject><subject>Cobra Cardiotoxin Proteins - chemical synthesis</subject><subject>Cobra Cardiotoxin Proteins - pharmacology</subject><subject>Cyclic</subject><subject>Humans</subject><subject>L1AD3</subject><subject>Leukemia - pathology</subject><subject>Leukemic</subject><subject>Leukocytes</subject><subject>Leukocytes - drug effects</subject><subject>Models, Molecular</subject><subject>Naja naja Atra</subject><subject>Peptide</subject><subject>Protein Conformation</subject><subject>Protein Structure, Tertiary</subject><subject>Rats</subject><subject>Structure-Activity Relationship</subject><subject>T-cell</subject><subject>T-Lymphocytes - drug effects</subject><issn>1095-6670</issn><issn>1099-0461</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtP3DAUha0KVF5d8AeQV0iVCFzbsR0vB9rhNSpdTFV2luPcoYa8Giei8--bYQZYVV3ds_jOp6tDyCGDUwbAzx7z_pSPQX4guwyMSSBVbOsly0QpDTtkL8ZHAJBGy49kh8lU8iyTu-R-Qv3Sl8HTFts-FHhCZ2zyRZzQUBeDx0jRdeWSxvBQR9osqGubtm9iiCNAfw2Vq2mJwxNWo2KeeCxLWoYa4wHZXrgy4qfN3Sc_pl_nF1fJ7O7y-mIyS7zgXCamkIaBZt74Qhkpcsckh2zhjDTImOPgM5ECz3UhIXeQa6e0Ys6INAVVoNgnx2tv2zW_B4y9rUJcveFqbIZolTLCZGD-C3LQRmi1Aj-vQd81MXa4sG0XKtctLQO72tuOe9uXvUf2aCMd8gqLd3Iz8AicrYHnUOLy3yZ7cz5_VSbrRog9_nlruO7JKi20tD-_Xdrp9_HR7FbaqfgLC2OWCA</recordid><startdate>2004</startdate><enddate>2004</enddate><creator>Smith, Charles A.</creator><creator>Hinman, Channing L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>2004</creationdate><title>A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines</title><author>Smith, Charles A. ; Hinman, Channing L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3225-9d591071c9cd6953ba15208fa959e11a20c83402b7d50ba0b7a6761a934406de3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Cardiotoxin</topic><topic>Caspases - drug effects</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Circular Dichroism</topic><topic>Cobra Cardiotoxin Proteins - chemical synthesis</topic><topic>Cobra Cardiotoxin Proteins - pharmacology</topic><topic>Cyclic</topic><topic>Humans</topic><topic>L1AD3</topic><topic>Leukemia - pathology</topic><topic>Leukemic</topic><topic>Leukocytes</topic><topic>Leukocytes - drug effects</topic><topic>Models, Molecular</topic><topic>Naja naja Atra</topic><topic>Peptide</topic><topic>Protein Conformation</topic><topic>Protein Structure, Tertiary</topic><topic>Rats</topic><topic>Structure-Activity Relationship</topic><topic>T-cell</topic><topic>T-Lymphocytes - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Charles A.</creatorcontrib><creatorcontrib>Hinman, Channing L.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of biochemical and molecular toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Charles A.</au><au>Hinman, Channing L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines</atitle><jtitle>Journal of biochemical and molecular toxicology</jtitle><addtitle>J. Biochem. Mol. Toxicol</addtitle><date>2004</date><risdate>2004</risdate><volume>18</volume><issue>4</issue><spage>204</spage><epage>220</epage><pages>204-220</pages><issn>1095-6670</issn><eissn>1099-0461</eissn><abstract>L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T‐cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:204–220, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20025</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15452885</pmid><doi>10.1002/jbt.20025</doi><tpages>17</tpages></addata></record> |
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subjects | Amino Acid Sequence Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Apoptosis - physiology Cardiotoxin Caspases - drug effects Cell Line Cell Line, Tumor Cell Survival - drug effects Circular Dichroism Cobra Cardiotoxin Proteins - chemical synthesis Cobra Cardiotoxin Proteins - pharmacology Cyclic Humans L1AD3 Leukemia - pathology Leukemic Leukocytes Leukocytes - drug effects Models, Molecular Naja naja Atra Peptide Protein Conformation Protein Structure, Tertiary Rats Structure-Activity Relationship T-cell T-Lymphocytes - drug effects |
title | A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T-cell lines |
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