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Research in Pharmaceutical Sciences، جلد ۱۴، شماره ۴، صفحات ۳۵۹-۳۶۸
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عنوان انگلیسی Improving the solubility, activity, and stability of reteplase using in silico design of new variants
چکیده انگلیسی مقاله Reteplase (recombinant plasminogen activator, r-PA) is a thrombolytic agent recombined from tissue-type plasminogen activator (t-PA), which has several prominent features such as strong thrombolytic ability and E. coli expressibility. Despite these outstanding features, it demonstrates reduced fibrin binding affinity, reduced stimulation of protease activity, and lower solubility, hence higher aggregation propensity, compared to t-PA. The present study was devoted to design r-PA variants with comparable structural stability, enhanced biological activity, and high solubility. For this purpose, computational molecular modeling techniques were utilized. The supercharging technique was applied for r-PA to designing new species of the protein. Based on the results from in silico evaluation of selected mutations in comparison to the wild-type r-PA, the designed supercharged mutant (S7 variant) exhibited augmented stability, decreased solvation energy, as well as enhanced binding affinity to fibrin. The data also implied increased plasminogen cleavage activity of the new variant. These findings have implications to therapies which involve removal of intravascular blood clots, including the treatment of acute myocardial infarction.
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نویسندگان مقاله | Hooria Seyedhosseini Ghaheh
2Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, I.R. Iran.


| Mohamad Reza Ganjalikhany
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, I.R. Iran.


| Parichehreh Yaghmaei
3Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.


| Morteza Pourfarzam
4Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.


| Hamid Mir Mohammad Sadeghi


نشانی اینترنتی http://rps.mui.ac.ir/index.php/jrps/article/view/1919
فایل مقاله اشکال در دسترسی به فایل - ./files/site1/rds_journals/115/article-115-1870960.pdf
کد مقاله (doi)
زبان مقاله منتشر شده en
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نوع مقاله منتشر شده Original Article
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