聚乙二醇化
体内
效力
体外
阿尔法(金融)
PEG比率
生物活性
化学
聚乙二醇
药理学
生物化学
医学
生物
财务
生物技术
护理部
经济
患者满意度
结构效度
作者
Yasuo Yoshioka,Yasuo Tsutsumi,Shinji Ikemizu,Yoko Yamamoto,Hiroko Shibata,Toshihide Nishibata,Yohei Mukai,Takayuki Okamoto,Madoka Taniai,Morio Kawamura,Yasuhiro Abe,Shinsaku Nakagawa,Satoshi Nagata,Yuriko Yamagata,Tadanori Mayumi
标识
DOI:10.1016/j.bbrc.2004.01.125
摘要
Recently, we created a lysine-deficient mutant tumor necrosis factor-alpha [mTNF-alpha-Lys(-)] with full bioactivity in vitro compared with wild-type TNF-alpha (wTNF-alpha), and site-specific PEGylation of mTNF-alpha-Lys(-) was found to selectively enhance its in vivo antitumor activity. In this study, we attempted to optimize this PEGylation of mTNF-alpha-Lys(-) to further improve its therapeutic potency. mTNF-alpha-Lys(-) was site-specifically modified at its N-terminus with linear polyethylene glycol (LPEG) or branched PEG (BPEG). While randomly mono-PEGylated wTNF-alpha (ran-LPEG5K-wTNF-alpha) with 5 kDa of LPEG (LPEG5K) had about only 4% in vitro bioactivity of wTNF-alpha, mono-PEGylated mTNF-alpha-Lys(-) [sp-PEG-mTNF-alpha-Lys(-)] with LPEG5K, LPEG20K, BPEG10K, and BPEG40K had 82%, 58%, 93%, and 65% bioactivities of mTNF-alpha-Lys(-), respectively. sp-LPEG-mTNF-alpha-Lys(-) and sp-BPEG10K-mTNF-alpha-Lys(-) had much superior antitumor activity to those of both unmodified TNF-alphas and ran-LPEG5K-wTNF-alpha, though sp-BPEG40K-mTNF-alpha-Lys(-) did not show in vivo antitumor activity. Thus, the molecular shape and weight of PEG may strongly influence the in vivo antitumor activity of sp-PEG-mTNF-alpha-Lys(-).
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