Abstract
A new class of methoxy-poly(ethylene glycol) (mPEG) derivatives having a cleavable group of oligo-lactic acid (OLA) was synthesized by ring opening polymerization of L-lactide using a terminal hydroxyl end of mPEG as an initiator. The synthesized mPEG derivatives had 0.8 and 3.6 lactic acid units based on the MALDI-TOF data. A terminal end group of mPEG-OLA was further activated with p-nitrophenyl chloroformate to produce mPEG-OLA-p-nitrophenyl carbonate (PC). mPEG-OLA-PC derivatives were conjugated to primary amine groups of recombinant human granulocyte-colony stimulating factor. PEGylated G-CSF conjugated with mPEG-OLA-PC derivatives consisted of native, mono-, di-, and tri-PEGylated species, and they did not show any apparent conformational changes even after PEGylation. When incubating in pH 7.4 buffer at 37°C for 2 days, mPEG-OLA-G-CSF conjugates liberated mPEG by cleaving the OLA spacer, resulting in the gradual regeneration of G-CSF.
| Original language | English |
|---|---|
| Pages (from-to) | 271-284 |
| Number of pages | 14 |
| Journal | Journal of Controlled Release |
| Volume | 89 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 29 2003 |
| Externally published | Yes |
Funding
This work was supported from the Ministry of Commerce, Industry and Energy (A00-961-5411-02-3-3), South Korea. We would like to thank the Mogam Research Institute for providing G-CSF.
| Funders | Funder number |
|---|---|
| Ministry of Commerce, Industry and Energy | A00-961-5411-02-3-3 |
Keywords
- Cleavable
- G-CSF
- Oligo-lactic acid
- PEG
- PEGylation