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
Hauptverfasser: Smith, Charles A., Hinman, Channing L.
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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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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). 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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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