PEGylation of alpha-momorcharin: synthesis and characterization of novel anti-tumor conjugates with therapeutic potential.
Alpha-momorcharin (alpha-MMC) is a ribosome-inactivating protein (RIP) with excellent cytotoxicity to tumor cells. However, its strong immunogenicity and short plasma half-life limit its clinical applications. To overcome this, we have to PEGylated alpha-MMC using a branched 20 kDa (mPEG) (2)-Lys-NHS. Homogeneous mono-, di- and tri-PEGylated alpha-MMCs were synthesized, purified and characterized. In vitro and in vivo analysis indicated that the serial PEG-conjugates preserved moderate anti-tumor activity with 36% acute toxicity and at most 66% immunogenicity decrease. These results suggested the potential application of alpha-MMC-PEG conjugates as an anti-tumor agent.
Bian
Xiaoxiao
X
Key Laboratory of Bio-Resources and Eco-Environment Ministry of Education/Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu, 610064, China.
Shen
Fubing
F
Chen
Yiwen
Y
Wang
Baoning
B
Deng
Mian
M
Meng
Yanfa
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D054788:Ribosome Inactivating Proteins / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C039582:MMC protein, Momordica charantia; D054788:Ribosome Inactivating Proteins