مدل سازی کوانتوم مکانیکی مهارکننده ایزوفتالایمیدی آنزیم بتا-سکرتاز: آنالیز تجزیه ای آمینو اسید

رزاقی اصل, نیما and عبادی, احمد and ادراکی, نجمه and شهابی پور, سارا and میری, رامین (1392) مدل سازی کوانتوم مکانیکی مهارکننده ایزوفتالایمیدی آنزیم بتا-سکرتاز: آنالیز تجزیه ای آمینو اسید. Medicinal Chemistry Research ــ 22 (7). pp. 3259-3269. شاپا 1054-2523

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Official URL: http://link.springer.com/article/10.1007/s00044-01...


Ab initio modeling of a potent isophthalamide-based BACE-1 inhibitor: amino acid decomposition analysis

English Abstract

β-Secretase or β-site amyloid precursor protein cleaving enzyme (BACE-1) is a membrane-associated aspartyl protease that catalyzes the first step in the formation of amyloid β plaques responsible for Alzheimer’s disease (AD). β-Secretase has been considered as a striking therapeutic target for AD. Recently, several attempts have been focused on the development of inhibitors of this key protease. Among small molecules, scaffolds based on isophthalamide derivatives have been reported as potent non-peptidic BACE-1 inhibitors. In the present study, interactions of a 5-(N-methylmethan-4-ylsulfonamido) isophthalamide-based scaffold with BACE-1 active site residues have been evaluated via the functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP). The complex ligand–receptor system including N1-(4-(cyclopropylamino)-3-hydroxy-1-phenylbutan-2-yl)-5-(N-methylmethan-4-ylsulfonamido)-N3(1-phenylethyl) isophthalamide (5HA) and 18 amino acids constructing BACE-1 active site exhibited H-bonds, π–π stacking, and Van der Waals interactions associated with total binding energy of −268.34 kcal/mol at B3LYP/Def2-SVP level. The outcomes of conformational analysis postulated that the studied isophthalamide-based structure might not necessarily interact with the active site of BACE-1 in its optimum geometric conformation.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نیما رزاقی اصل
نویسنده :احمد عبادی
نویسنده :نجمه ادراکی
نویسنده :سارا شهابی پور
نویسنده مسئول :رامین میری
Additional Information:Impact Factor : 1.612 Indexed in: Science Citation Index Expanded (SciSearch), Journal Citation Reports/Science Edition, SCOPUS, EMBASE, Chemical Abstracts Service (CAS), Google Scholar, CAB International, Academic OneFile, AGRICOLA, Biological Abstracts, BIOSIS, CAB Abstracts, ChemWeb, Chimica, Current Contents/ Life Sciences, Gale, Global Health, OCLC, Reaxys, SCImago, Summon by Serial Solutions
Uncontrolled Keywords:آلزایمر ، بتاسکرتاز ، ایزوفتالامید
کلیدواژه ها (انگلیسی):Alzheimer , Beta secretase , Isophthalamide , B3LYP
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:5394
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:14 Dec 1392 13:44
Last Modified:14 Dec 1392 13:44

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