| Human uridine-cytidine kinase phosphorylation of ribavirin: a convenient method for activation of ribavirin for conjugation to proteins. | |
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MedLine Citation:
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PMID: 18080217 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ribavirin is a synthetic nucleoside analog that is used for the treatment of hepatitis C virus (HCV) infection. Its primary toxicity is hemolytic anemia, which sometimes necessitates dose reduction or discontinuation of therapy. Selective delivery of ribavirin into liver cells would be desirable to enhance its antiviral activity and avoid systemic side effects. One approach to liver-specific targeting is conjugation of the ribavirin with asialoglycoprotein that is taken up specifically by liver cells. Human uridine-cytidine kinase-1 (UCK-1) was used for ribavirin phosphorylation to its monophosphate form. 1-Ethyl-3-diisopropylaminocarbodiimide (EDC) was used as a coupling agent. The best results were obtained using direct conjugation protocol with a molar ratio of 6.5 ribavirin monophosphate (RMP) molecules per one asialoorosomucoid (AsOR) molecule. Our findings show that ribavirin is a potential substrate of UCK-1, and RMP formed could be chemically coupled to AsOR to form a conjugate for liver specific targeting. |
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Authors:
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Lucija Virovic Jukic; Marko Duvnjak; Catherine H Wu; George Y Wu |
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Publication Detail:
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Type: Journal Article Date: 2007-12-13 |
Journal Detail:
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Title: Journal of biomedical science Volume: 15 ISSN: 1423-0127 ISO Abbreviation: J. Biomed. Sci. Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-25 Completed Date: 2008-04-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421567 Medline TA: J Biomed Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 205-13 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Division of Gastroenterology and Hepatology, Charity Sisters University Hospital, Vinogradska cesta 29, 10 000, Zagreb, Croatia, lucija.virovic@zg.t-com.hr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anemia, Hemolytic
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chemically induced,
enzymology Asialoglycoproteins / chemistry*, therapeutic use Drug Delivery Systems* Hepacivirus Hepatitis C / complications, enzymology* Humans Liver / enzymology*, virology Nucleoside-Phosphate Kinase / chemistry*, metabolism Orosomucoid / analogs & derivatives*, chemistry, therapeutic use Phosphorylation Ribavirin / adverse effects, chemistry*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Asialoglycoproteins; 0/Orosomucoid; 0/asialoorosomucoid; 36791-04-5/Ribavirin; EC 2.7.4.14/cytidylate kinase; EC 2.7.4.4/Nucleoside-Phosphate Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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