Methoxy poly (ethylene glycol) thiosulfonate: new activated polymer derivatives for thiol-specific modification

Thiol-reactive methoxy poly (ethylene glycol) (mPEG) derivatives, mPEG methanethiosulfonate (mPEG-MTS) and mPEG phenylthiosulfonate (mPEG-PTS), were synthesized by one-step S-alkylation of mPEG-halide with the corresponding sodium thiosulfonate. These functionalized polymers were fully characterized by H-1 NMR, C-13 NMR, GPC as well as MALDI-TOF. To demonstrate the potential application of mPEG-MTS and mPEG-PTS, papain and recombinant human granulocyte colony-stimulating factor (rhG-CSF) were used as prototype protein for thiol-selective PEGylation. The PEGylated products were verified by one or more of the following methods: SDS-PAGE, HPLC, HPSEC as well as MALDI-TOF. Compared with native rhG-CSF, the PEGylated rhG-CSF was further characterized by in vitro cell proliferative assay and preserved 59% biological activity. Furthermore, mPEG20k-MTS was used to modify BSA nanoparticles coated with thiol groups. FT-IR and zeta-potential assay demonstrated that mPEG thiosulfonate can be effectively immobilized at the nanoparticles' surface via disulfide linkage to form hydrophilic and neutral corona. Therefore, we have demonstrated thiol-selective PEG derivatives, endowed with unusual versatility, for practical use and potential exploitation. Copyright (C) 2009 John Wiley & Sons, Ltd.