کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584524 | 981334 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Solid-phase synthesis of 5â²-triphosphate 2â²-5â²-oligoadenylates analogs with 3â²-O-biolabile groups and their evaluation as RNase L activators and antiviral drugs
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
5â²-Triphosphate 2â²-5â²-oligoadenylate (2-5A) is the central player in the 2-5A system that is an innate immunity pathway in response to the presence of infectious agents. Intracellular endoribonuclease RNase L activated by 2-5A cleaves viral and cellular RNA resulting in apoptosis. The major limitations of 2-5A for therapeutic applications is the short biological half-life and poor cellular uptake. Modification of 2-5A with biolabile and lipophilic groups that facilitate its uptake, increase its in vivo stability and release the parent 2-5A drug in an intact form offer an alternative approach to therapeutic use of 2-5A. Here we have synthesized the trimeric and tetrameric 2-5A species bearing hydrophobic and enzymolabile pivaloyloxymethyl groups at 3â²-positions and a triphosphate at the 5â²-end. Both analogs were able to activate RNase L and the production of the trimer 2-5A (the most active) was scaled up to the milligram scale for antiviral evaluation in cells infected by influenza virus or respiratory syncytial virus. The trimer analog demonstrated some significant antiviral activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 17, 1 September 2013, Pages 5461-5469
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 17, 1 September 2013, Pages 5461-5469
نویسندگان
Yann Thillier, Sarah K. Stevens, Christabel Moy, Joshua Taylor, Jean-Jacques Vasseur, Leonid Beigelman, Françoise Debart,