G. Peng, Xin Pan, Haiyan Hu
Feb 1, 2019
Citations
0
Influential Citations
4
Citations
Quality indicators
Journal
Journal of Drug Delivery Science and Technology
Abstract
Abstract Covalent attachment of polyethylene glycol (PEG) to peptides and proteins has been used to increase the clinical efficacy and circulation half-life of biopharmaceuticals. The purpose of this study was to enhance the half-life of an important immune-modulating agent, Thymosin alpha 1 (Tα1), using site-specific PEGylation. A novel N-terminal modified Tα1 (Mal-Tα1) was constituted by condensing the N-terminal amino group of Tα1 with 3-maleimidopropionic acid (Mal). Then, Mal-Tα1 was site-specifically conjugated with methoxy polyethylene glycol thiol (mPEG-SH) under mild conditions to form mPEG-Mal-Tα1. The conjugation efficiency was greater than 95%. mPEG-Mal-Tα1 was stable in the presence of 2-mercaptoethanol and exhibited significantly increased immunoactivity compared to Tα1 in mice. The terminal half-life (t1/2β) of mPEG-Mal-Tα1 was 2.5 times longer than that of mPEG-Cys-Tα1 (PEGylation product of mPEG-Mal conjugated with Cysteine-Tα1) in rats. These results demonstrate that site-specific PEGylation of N-terminal Mal-Tα1 is a promising strategy for enhancing the circulation t1/2β of Tα1 compared to Cysteine-Tα1.