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Site‐directed PEGylations of Thymosin α 1 Analogs and Evaluation of Their Immunoactivity
Author(s) -
QIE Jiankun,
MA Jinbo,
WANG Liangyou,
XU Xiaoyu,
ZHOU Wenxia,
QI Chunhui,
ZHAO Xiunan,
ZHANG Yongxiang,
LIU Keliang
Publication year - 2009
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.200990134
Subject(s) - pegylation , chemistry , peptide , maleimide , thymosin , residue (chemistry) , cysteine , peg ratio , reagent , combinatorial chemistry , biochemistry , biophysics , stereochemistry , polyethylene glycol , organic chemistry , enzyme , finance , economics , biology
PEGylation is an effective way to improve the pharmacokinetic profiles of pharmaceutical proteins or peptides. But the relatively large and long PEG chains would be likely to shelter the active site of a small peptide because of its small size, compared with a protein. Therefore, the positions and numbers of PEGylation are crucial for the bioactivity of a PEGylated peptide. To elucidate the relationship between the PEGylated positions and bioactivity of a peptide drug, site‐specific PEGylations were performed on Zadaxin (Thymosin α 1, T α 1), which is a pharmaceutical peptide with an α ‐helix region, a β ‐turn region, and random coils. Site‐specific mono‐PEGylations of T α 1 in different conformational regions were realized through introducing one cysteine residue into the desired positions of the peptide, followed by a coupling reaction with a thiol‐attached maleimide‐PEG reagent. Primary data from IFN‐ γ production of splenocytes induced by Con A showed that the influence of PEGylation on Zadaxin was position‐dependent, and mostly, positive effects were observed after PEGylation, which indicated that the position of PEGylation is important for maintaining the bioactivity of a peptide.