کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10584087 981318 2013 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of a pharmacophore model for the catecholamine release-inhibitory peptide catestatin: Virtual screening and functional testing identify novel small molecule therapeutics of hypertension
ترجمه فارسی عنوان
توسعه یک مدل فارماکوفور برای کاستاتین پپتیدی مهارکننده کاتچولامین: غربالگری مجازی و تست عملکردی، شناسایی داروهای جدید مولکول های کوچک فشار خون بالا
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی
The endogenous catecholamine release-inhibitory peptide catestatin (CST) regulates events leading to hypertension and cardiovascular disease. Earlier we studied the structure of CST by NMR, molecular modeling, and amino acid scanning mutagenesis. That structure has now been exploited for elucidation of interface pharmacophores that mediate binding of CST to its target, with consequent secretory inhibition. Designed pharmacophore models allowed screening of 3D structural domains. Selected compounds were tested on both cultured catecholaminergic cells and an in vivo model of hypertension; in each case, the candidates showed substantial mimicry of native CST actions, with preserved or enhanced potency and specificity. The approach and compounds have thus enabled rational design of novel drug candidates for treatment of hypertension or autonomic dysfunction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 18, 15 September 2013, Pages 5855-5869
نویسندگان
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