کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361562 981466 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of novel ligands for the RNA pseudoknot that regulate −1 ribosomal frameshifting
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Identification of novel ligands for the RNA pseudoknot that regulate −1 ribosomal frameshifting
چکیده انگلیسی

In many viruses, −1 ribosomal frameshifting (−1RF) regulates synthesis of proteins and is crucial for virus production. An RNA pseudoknot is one of the essential components of the viral −1RF system. Thermodynamic or kinetic control of pseudoknot folding may be important in regulating the efficiency of −1RF. Thus, small molecules that interact with viral RNA pseudoknots may disrupt the −1RF system and show antiviral activity. In this study, we conducted virtual screening of a chemical database targeting the X-ray crystal structure of RNA pseudoknot complexed with biotin to identify ligands that may regulate an −1RF system containing biotin-aptamer as an RNA pseudoknot component. After docking screening of about 80,000 compounds, 58 high-ranked hits were selected and their activities were examined by in vitro and cell-based −1 frameshifting assays. Six compounds increased the efficiency of −1 frameshifting, and these are novel small molecule compounds that regulate the −1RF.

An RNA pseudoknot is one of the essential components of the viral −1 ribosomal frameshifting (−1RF) system. The control of pseudoknot stability is important in regulating the efficiency of −1RF. We conducted the virtual screening of a chemical database targeting the X-ray crystal structure of biotin-bound RNA pseudoknot to identify ligands that may regulate an −1RF system containing biotin-aptamer as an RNA pseudoknot component. After docking screening of about 80,000 compounds, 58 high-ranked hits were selected and their activities were examined by in vitro and cell-based −1 frameshifting assays. Six compounds increased the efficiency of −1 frameshifting, and these are novel small molecule compounds that regulate the −1RF.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 8, 15 April 2008, Pages 4676–4684
نویسندگان
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