单修饰重组水蛭素的设计,制备及体外生物活性测定

Q95; Hirudin,the most potent inhibitor of thrombin found in nature,has a short half-life in serum,which significantly limits its clinical application as an anticoagulant. Recently,PEGylation has been commonly used as an effective method to prolong its half-life in serum. In contrast to the nonspecif...

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Bibliographic Details
Published in中国化学工程学报（英文版） Vol. 15; no. 6; pp. 775 - 780
Main Authors 侯蓓蓓, 李世荣, 李晓晖, 修志龙
Format Journal Article
LanguageChinese
Published Department of Bioscience & Biotechnology,Dalian University of Technology,Dalian 116024,China 2007
Subjects
histidine residues
SC-mPEG
anticoagulant activity
pH
r-hirudin
mono-PEGylation
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ISSN1004-9541

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Summary:Q95; Hirudin,the most potent inhibitor of thrombin found in nature,has a short half-life in serum,which significantly limits its clinical application as an anticoagulant. Recently,PEGylation has been commonly used as an effective method to prolong its half-life in serum. In contrast to the nonspecific PEGylation under basic conditions that targets lysine residues randomly,PEGylation sites under mildly acidic conditions preferably targets histidine residues,and there is only one histidine residue at 51 in r-hirudin; therefore,succinimidyl carbonyl methoxy polyethylene glycol (SC-mPEG,20000) was attached to r-hirudin at mildly acidic pH to favor the formation of monoPEGylated r-hirudin. The reaction mixture with high mono-PEGylated ratio was easily separated by a one-step ion-exchange chromatographic (IEC) procedure. Approximately 79.71% of the mono-PEGylated r-hirudin was PEGylated at His51,which showed that the acidic PEGylation operation prevented the PEGylation of active center (Lys47) of r-hirudin in princ
ISSN:1004-9541