Studies of bioactivity, conformation and pharmacokinetic profiles of site-specific PEGylated thymosin alpha 1 derivatives.
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.
Qie
Jiankun
J
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, PR China.
Ma
Jinbo
J
Wang
Liangyou
L
Xu
Xiaoyu
X
Zheng
Jianquan
J
Dong
Sijian
S
Xie
Jianwei
J
Sun
Huixian
H
Zhou
Wenxia
W
Qi
Chunhui
C
Zhao
Xiunan
X
Zhang
Yongxiang
Y
Liu
Keliang
K
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D008301:Maleimides / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D011487:Protein Conformation; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D008301:Maleimides; C043592:maleimide; D011092:Polyethylene Glycols; D013947:Thymosin; C028210:monomethoxypolyethylene glycol; D000077596:Thymalfasin