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[期刊论文]
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Design of a Modular Immunotoxin Connected by Polyionic Adapter Peptides
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作 者:
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Martin Kleinschmidt;Rainer Rudolph;Hauke Lilie;
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出版年:2003
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页 码:445 - 452
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出版社:Elsevier BV
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摘 要:
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Immunotoxins are genetically engineered fusion proteins of an antibody Fv fragment and a toxin from bacteria or plants, which function as anti-cancer therapeutics. Here, we describe a new generation of immunotoxins in which both proteins do not form a single fusion protein but are coupled specifically via cysteine-containing polyionic fusion peptides. The engineered Pseudomonas exotoxin PE38 was N-terminally fused to the peptide E8C. In combination with the disulfide-stabilized Fv fragment of the tumor-specific antibody B3, which was extended by the peptide R8CP, the fusion peptides ensured a specific and covalent coupling of the Fv fragment and the toxin. The resulting immunotoxin was as active and as specific as an immunotoxin consisting of a fusion protein of the same antibody fragment connected to the toxin.
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关键字:
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Fv fragment;exotoxin;disulfide bond;polyionic peptides;FACS;B3(dsFv)PE38, genetically fused immunotoxin of the disulfide-stabilized Fv fragment of the antibody B3 and the Pseudomonas exotoxin derivative PE38;B3-PE38, conjugated immunotoxin composed of dsFv-B3-R8C and E8C-PE38;dsFv-B3-R8C, disulfide-stabilized Fv fragment of the antibody B3 extended at the C terminus of the VH domain by the peptide R8CP;GSH, reduced glutathione;GSSG, oxidized glutathione;PE38, truncated version of the Pseudomonas exotoxin consisting of a part of the domain Ib and domains II and III;GST, glutathione-S-transferase
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所属期刊
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ISSN: 0022-2836
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来自:Elsevier BV
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