PEGylation of á-momorcharin retained its anti-tumor activity with reduced potency <i>in vitro</i> and <i>in vivo</i>

Abstract

α-Momorcharin (α-MMC) is the ribosome inactivating protein (RIPs) found to possess antitumor activity. However, acute toxicity and short plasma half-life were the major side effects preventing further clinical trial. To overcome this, á-MMC was further coupled to polyethylene glycol with di-molecular size of 20 kDa (PEG) using the cysteine residues, namely α-MMC-PEG. The median effect concentrations (EC₅₀) were estimated as 100 and 130 µg, for α-MMC and α-MMC-PEG in vitro, respectively. Results show that the anti-tumor activity of α-MMC-PEG decreased by about 30% in vitro. This sensitivity increase of 50% from α-MMC to α-MMC-PEG reached 5 µg and was kept at 4°C for three months, and the thermal and pH-stability of the α-MMC-PEG was also strengthened. The in vivo study showed that the anti-tumor activity of pegylated á-MMC enhanced the activity of anti-tumor activity as compared to natural α-MMC. These results suggest that α-MMC-PEG may be useful for the therapy of tumor.

Key words: α-Momorcharin, acute toxicity, DNA glycosylase, N-glycosidase, stability.