PEGylation of G-CSF in organic solvent markedly increase the efficacy and reactivity through protein unfolding, hydrolysis inhibition and solvent effect.
作者： Fei Peng , Yongdong Liu , Xiunan Li , Lijing Sun , Dawei Zhao
DOI: 10.1016/J.JBIOTEC.2013.10.037
关键词:
摘要: Previous studies demonstrated that hydrophobic proteins could be PEGylated in organic phase rather than water phase. It is still not known what the difference for a hydrophilic protein's PEGylation these two different phases. In this study, granulocyte colony stimulating factor (G-CSF) was dissolved neat dimethyl sulfoxide (DMSO) and PEGylated. comparison with solution, degree solvent increased by 33% 42% PEG-maleimide (MAL-PEG) PEG-succinimidyl carbonate (SC-PEG) respectively. Structure analysis revealed protein unfolded DMSO, which make sites of G-CSF easily accessible. The hydrolysis half-life solution 40 min 9 h SC-PEG MAL-PEG However, DMSO solvent, PEGs were very stable no detected. Stopped-flow conjugation speed 1.6 x 10(4) 2 10(2) times faster those aqueous solution. remarkable acceleration mainly attributed to an increase nucleophilicity DMSO. results study referential industrial application where cost PEG reagents reaction on large scale are important. (C) 2013 Elsevier B.V. All rights reserved.
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