کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10591089 | 981739 | 2014 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HDX reveals unique fragment ligands for the vitamin D receptor
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Modulation of the vitamin D receptor (VDR) with a ligand has the potential to be useful for the oral treatment of osteoporosis. One component of our lead generation strategy to identify synthetic ligands for VDR included a fragment based drug design approach. Screening of ligands in a VDR fluorescence polarization assay and a RXR/VDR conformation sensing assay resulted in the identification of multiple fragment hits (lean >0.30). These fragment scaffolds were subsequently evaluated for interaction with the VDR ligand binding domain using hydrogen-deuterium exchange (HDX) mass spectrometry. Significant protection of H/D exchange was observed for some fragments in helixes 3, 7, and 8 of the ligand binding domain, regions which are similar to those seen for the natural hormone VD3. The fragments appear to mimic the A-ring of VD3 thereby providing viable starting points for synthetic expansion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 15, 1 August 2014, Pages 3459-3463
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 15, 1 August 2014, Pages 3459-3463
نویسندگان
Matthew W. Carson, Jun Zhang, Michael J. Chalmers, Wayne P. Bocchinfuso, Karol D. Holifield, Thierry Masquelin, Ryan E. Stites, Keith R. Stayrook, Patrick R. Griffin, Jeffery A. Dodge,