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Current Topics in Peptide & Protein Research   Volumes    Volume 6 
Bioconjugation of proteins with polymeric modifiers for improvement of their therapeutic efficacy
Yohei Mukai, Yasuo Tsutsumi, Yasuo Yoshioka, Tadanori Mayumi
Pages: 167 - 176
Number of pages: 10
Current Topics in Peptide & Protein Research
Volume 6 

Copyright © 2004 Research Trends. All rights reserved


Following recent marked advances in genome and proteomic analysis, the therapeutic application of bioactive proteins, such as newly identified proteins, has been highly expected. However, most of these proteins are limited in their clinical application because of unexpectedly low therapeutic effects and toxic side-effects. Since almost all of these bioactive proteins are quite unstable in vivo, their clinical use as a therapeutic agent requires frequent administration and high doses which result in impair homeostasis in vivo and cause severe adverse effects. One of the most effective drug delivery system (DDS) to overcome these problems is bioconjugation of proteins with water-soluble polymeric modifiers such as polyethylene glycol (PEG). In this review, we discussed recent progress in bioconjugation as a polymeric DDS, in making our research to be example. At first, we showed that the optimal PEGylation of tumor necrosis factor-alpha (TNF-a), as an antitumor agent and selective enhancer of tumor vascular permeability, improved its stability in vivo and selectively enhanced its therapeutic window. Additionally, we discussed the usefulness of polyvinylpyrrolidone (PVP) as a polymeric modifier for achieving long plasma half-lives of proteins and PVP derivatives with the tissue-targeting capability. We, then, showed the application of divinyl ether and maleic anhydride copolymer (DIVEMA), which has intrinsic antitumor activity as a synthetic biological response modifier, for the bioconjugation of TNF-a. Finally, we showed the novel bioconjugation method without decrease of bioactivity. This review will provide us useful information for optimization of bioconjugated protein therapy.

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