کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1375559 981941 2009 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design and synthesis of new hydroxyethylamines as inhibitors of d-alanyl-d-lactate ligase (VanA) and d-alanyl-d-alanine ligase (DdlB)
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Design and synthesis of new hydroxyethylamines as inhibitors of d-alanyl-d-lactate ligase (VanA) and d-alanyl-d-alanine ligase (DdlB)
چکیده انگلیسی

The Van enzymes are ATP-dependant ligases responsible for resistance to vancomycin in Staphylococcus aureus and Enteroccoccus species. The de novo molecular design programme SPROUT was used in conjunction with the X-ray crystal structure of Enterococcus faeciumd-alanyl-d-lactate ligase (VanA) to design new putative inhibitors based on a hydroxyethylamine template. The two best ranked structures were selected and efficient syntheses developed. The inhibitory activities of these molecules were determined on E. faecium VanA, and due to structural similarity and a common reaction mechanism, also on d-Ala-d-Ala ligase (DdlB) from Escherichia coli. The phosphate group attached to the hydroxyl moiety of the hydroxyethylamine isostere within these systems is essential for their inhibitory activity against both VanA and DdlB.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 5, 1 March 2009, Pages 1376–1379
نویسندگان
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