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Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics

Paper ID Volume ID Publish Year Pages File Format Full-Text
14087 1144 2007 7 PDF Available
Title
Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics
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 (M1, M2 and M3) and two PEGylated TCS muteins (PM1 and PM2) 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.

Keywords
TCS, trichosanthin; RIP, ribosome-inactivating protein; PEG, polyethylene glycol; nTCS, natural TCS; wTCS, wild-type TCS; mTCS, mutant TCSTrichosanthin; Ribosome-inactivating protein; Site-directed PEGylation; Immunogenicity; Pharmacokinetics
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Effect of site-directed PEGylation of trichosanthin on its biological activity, immunogenicity, and pharmacokinetics
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomolecular Engineering - Volume 24, Issue 6, December 2007, Pages 643–649
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us