| Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics. | |
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MedLine Citation:
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PMID: 18023612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) with multiple biological and pharmacological activities. It has been approved effective in the clinical treatment of AIDS and tumor, but its strong immunogenicity and short plasma half-life have limited the clinical administration. To reduce the immunogenicity and prolong the plasma half-life of this compound, three TCS muteins (M(1), M(2) and M(3)) and two PEGylated TCS muteins (PM(1) and PM(2)) were constructed by site-directed mutagenesis and PEGylation, respectively. Compared with the unmodified TCS, both PEGylated TCS showed a 3- to 4-fold decrease in immunogenicity, a 0.5- to 0.8-fold decrease in non-specific toxicity, and a 4.5- to 6-fold increase in plasma half-life. But there is a problem of activity reduction. The increased circulating half-life in vivo may compensate for the reduced activity. Together with the other benefits of PEGylation such as reduced immunogenicity and toxicity, it is worthwhile to further explore the potential application of the PEGylated TCS as a better therapeutic agent for AIDS and tumor. |
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Authors:
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Qunxing An; Yingfeng Lei; Ning Jia; Xianqing Zhang; Yinlan Bai; Jing Yi; Rui Chen; Aijun Xia; Jing Yang; Sanhua Wei; Xiaodong Cheng; Ailing Fan; Shijie Mu; Zhikai Xu |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-10-23 |
Journal Detail:
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Title: Biomolecular engineering Volume: 24 ISSN: 1389-0344 ISO Abbreviation: Biomol. Eng. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-26 Completed Date: 2008-04-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100928062 Medline TA: Biomol Eng Country: Netherlands |
Other Details:
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Languages: eng Pagination: 643-9 Citation Subset: IM |
Affiliation:
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Department of Blood Transfusion, Xijing Hospital, Fourth Military Medical University, Xi'an 710033, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-HIV Agents / adverse effects, immunology, pharmacology Antineoplastic Agents, Phytogenic / adverse effects, immunology, pharmacology Mice Mice, Inbred BALB C Mutagenesis, Site-Directed Polyethylene Glycols / chemistry* Ribosome Inactivating Proteins / adverse effects, genetics, immunology*, pharmacology Trichosanthin / adverse effects, genetics, immunology*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Anti-HIV Agents; 0/Antineoplastic Agents, Phytogenic; 0/Polyethylene Glycols; 60318-52-7/Trichosanthin; EC 3.2.2.22/Ribosome Inactivating Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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