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Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG

Paper ID Volume ID Publish Year Pages File Format Full-Text
35900 45113 2007 7 PDF Available
Title
Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG
Abstract

rhG-CSF (recombinant human granulocyte-colony stimulating factor) was chemically conjugated with branched mPEG (monomethoxyl polyethylene glycols), which was synthesized by a new method with the reaction between highly reactive carboxymethylated PEG succinimidy ester (SCM-PEG) and strongly nuclophilicitic amino group of lysine ethyl ester hydrochloride (lys-OEt 2HCl) in methylene chloride. The monopegylated rhG-CSF with branched mPEG (mono-B-pegylated rhG-CSF) was purified by one-step cationic exchange chromatography and characterized with HPSEC (high performance size exclusion chromatography), SDS-PAGE and MALDI-TOF MS. A monopegylated rhG-CSF with linear mPEG (mono-L-pegylated rhG-CSF) was also prepared to investigate the effect of structural difference on bioactivities. The comparison of mono-B-pegylated and mono-L-pegylated rhG-CSF was carried out on in vitro bioactivity, in vivo half-life time and Fr (relative bioavailability). The results showed that the in vitro relative bioactivity decreased to 54%, 61% for mono-B-pegylated and mono-L-pegylated rhG-CSF, respectively. However, compared with the unmodified rhG-CSF, the mono-B-pegylated and mono-L-pegylated rhG-CSF prolonged plasma half-life time from 40 min to 190 min and 145 min, respectively. The Fr was 2.01 for the mono-B-pegylated rhG-CSF, while 1.32 for the mono-L-pegylated. These results suggested that the mono-B-pegylated rhG-CSF is more effective in improving pharmacokinetic performance than the mono-L-pegylated and unmodified rhG-CSF.

Keywords
Synthesis; Branched mPEG; rhG-CSF; Monopegylated rhG-CSF; Half-life time; Relative bioavailability
First Page Preview
Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG
Publisher
Database: Elsevier - ScienceDirect
Journal: Process Biochemistry - Volume 42, Issue 12, December 2007, Pages 1625–1631
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering