Biophysical and Biological Characterization of PEGylated Recombinant Human Endostatin (M2 ES).
Guo, L.; Xu, B.; Zhou, D. (...)
【来源】：Clinical and experimental pharmacology & physiology, 2019,
【摘要】：Recombinant human endostatin (MES), showing potent inhibition on angiogenesis and tumor growth, has great potential as therapeutic agents for tumor. The aim of this study was to evaluate the biophysical and biological characterization of PEGylated recombinant human endostatin (M2 ES). MES was mono-PEGylated by conjugation with methoxy polyethylene glycol aldehyde (mPEG-ALD), and the modification site was identified by digested peptide mapping and MALDI-TOF-MS. The purity was assessed by SDS-PAGE, HPLC, and capillary zone electrophoresis. The physicochemical property was analyzed through fluorescence spectroscopy, and circular dichroism. The bioactivity and anti-tumor efficacy of M2 ES were evaluated using an in vitro endothelial cell migration model and a nunll-mouse xenograft model of a prostatic cancer, respectively. M2 ES molecules contain a single 20 kDa mPEG-ALD molecule conjugated at the N-terminal portion of MES. The purity of M2 ES was greater than 98%. The physicochemical analysis demonstrated that PEGylation does not change the secondary and tertiary structure of MES. Notably, M2 ES retards endothelial cell migration and tumor growth when compared to control group. These biophysical and biological characterization study data contribute to the initiation of the ongoing clinical study. This article is protected by copyright. All rights reserved.