國家衛生研究院 NHRI:Item 3990099045/3609
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    題名: Thiopurine analogue inhibitors of severe acute respiratory syndrome-coronavirus papain-like protease, a deubiquitinating and deISGylating enzyme
    作者: Chen, X;Chou, CY;Chang, GG
    貢獻者: Division of Biotechnology and Pharmaceutical Research
    摘要: In the search for effective therapeutics against severe acute respiratory syndrome (SARS), 6-mercaptopurine (6MP) and 6-thioguanine (6TG) were found to be specific inhibitors for the SARS-coronavirus (CoV) papain-like protease (PLpro), a cysteine protease with deubiquitinating and deISGylating activity. 6MP and 6TG have long been used in cancer chemotherapy for treatment of acute lymphoblastic or myeloblastic leukaemia. Development and optimization of 6MP and 6TG will not only be important for antiviral studies, but also for further elucidating the biological functions of cellular deubiquitinating enzymes (DUBs) and deISGylating enzymes. So far, several crystal structures of cellular DUBs have been solved. Structure comparison has been carried out to search for DUBs with a similar structure to that of PLpro, and we have tried to dock 6MP and 6TG into these DUBs to investigate the potential use of 6MP and 6TG as cellular DUB inhibitors. The best docking score and binding energy for 6MP and 6TG is against ubiquitin-specific protease (USP)14, suggesting that 6MP and 6TG are potential inhibitors of USP14. Finding new usages for old drugs will speed up the process of drug discovery and substantially reduce the cost of drug development.
    日期: 2009
    關聯: Antiviral Chemistry and Chemotherapy. 2009;19(4):151-156.
    Link to: http://www.intmedpress.com/journals/avcc/abstract.cfm?id=206&pid=92
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=65549141218
    顯示於類別:[陳新(2002-2015)] 期刊論文

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