کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1355545 981026 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines
ترجمه فارسی عنوان
بهینه سازی تحت هدایت سرینگولین ها مهار کننده های پروتئازوما قوی با فعالیت در برابر سلول های سلولی لوسمی
کلمات کلیدی
سرینگولینها، پروتئازوم، لوسمی، مهار کننده ها
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 23, Issue 18, 15 September 2015, Pages 6218–6222
نویسندگان
, , , , ,