Studies of bioactivity, conformation and pharmacokinetic profiles of site-specific PEGylated thymosin alpha 1 derivatives.

Drug metabolism letters2007PMID: 19356048

Plain Language Summary

Scientists attached polyethylene glycol (PEG) molecules to specific sites on thymosin alpha-1 to improve its stability and duration in the body. PEGylation at different structural regions significantly affected the peptide's shape and how long it lasted in the bloodstream but had little impact on its immune-stimulating activity, suggesting this modification could enhance the drug's pharmacological profile.

Abstract

Site-specific mono-PEGylations were performed in different conformational regions of Thymosin alpha 1 (T alpha 1) by introducing one cysteine residue into the chosen site and coupling with thiol-specific mPEG-MAL reagent. Results demonstrated that PEGylated sites and regions influenced the conformations and pharmacokinetic profiles of the peptide greatly with following order: alpha-helix, beta-turn, random coil and terminals, but little on the immunoactivity.

Authors

Qie, Jiankun; Ma, Jinbo; Wang, Liangyou; Xu, Xiaoyu; Zheng, Jianquan; Dong, Sijian; Xie, Jianwei; Sun, Huixian; Zhou, Wenxia; Qi, Chunhui; Zhao, Xiunan; Zhang, Yongxiang; Liu, Keliang