کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10825784 | 1064673 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Integrating virtual and biochemical screening for protein tyrosine phosphatase inhibitor discovery
ترجمه فارسی عنوان
یکپارچه سازی غربالگری مجازی و بیوشیمیایی برای کشف مهارکننده پروتئین تروستین فسفاتاز
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کلمات کلیدی
HTSpTyrpNPPRCCPTPσPTPPDBDTTpara-nitrophenyl phosphate - para-nitrofenyl phosphateROS - ROSInhibitor - بازدارندهdithiothreitol - دیتیوتریتولhigh-throughput screen - صفحه نمایش با قدرت بالاVirtual screen - صفحه نمایش مجازیVirtual screening - غربالگری مجازیphosphotyrosine - فسفاتیزینSmall molecule - مولکول های کوچکProtein Data Bank - پروتئین بانک اطلاعاتیProtein tyrosine phosphatase - پروتئین تیروزین فسفاتازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Protein tyrosine phosphatases (PTPs) represent an important class of enzymes that mediate signal transduction and control diverse aspects of cell behavior. The importance of their activity is exemplified by their significant contribution to disease etiology with over half of all human PTP genes implicated in at least one disease. Small molecule inhibitors targeting individual PTPs are important biological tools, and are needed to fully characterize the function of these enzymes. Moreover, potent and selective PTP inhibitors hold the promise to transform the treatment of many diseases. While numerous methods exist to develop PTP-directed small molecules, we have found that complimentary use of both virtual (in silico) and biochemical (in vitro) screening approaches expedite compound identification and drug development. Here, we summarize methods pertinent to our work and others. Focusing on specific challenges and successes we have experienced, we discuss the considerable caution that must be taken to avoid enrichment of inhibitors that function by non-selective oxidation. We also discuss the utility of using “open” PTP structures to identify active-site directed compounds, a rather unconventional choice for virtual screening. When integrated closely, virtual and biochemical screening can be used in a productive workflow to identify small molecules targeting PTPs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 65, Issue 2, 15 January 2014, Pages 219-228
Journal: Methods - Volume 65, Issue 2, 15 January 2014, Pages 219-228
نویسندگان
Katie R. Martin, Pooja Narang, José L. Medina-Franco, Nathalie Meurice, Jeffrey P. MacKeigan,