| Literature DB >> 18023612 |
Qunxing An1, 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.
Abstract
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.Entities:
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Year: 2007 PMID： 18023612 DOI： 10.1016/j.bioeng.2007.10.002
Source DB: PubMed Journal: Biomol Eng ISSN： 1389-0344