کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10595780 981876 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and evaluation of dual site inhibitors of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis and evaluation of dual site inhibitors of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase
چکیده انگلیسی
3-Deoxy-d-arabino-heptulosonate 7-phosphate (DAH7P) synthase catalyses the first step of the shikimate pathway for the biosynthesis of aromatic compounds. Enzymes of this pathway have been identified as potential targets for drug design. The reaction catalysed by DAH7P synthase is an aldol condensation between phosphoenolpyruvate (PEP) and d-erythrose 4-phosphate (E4P). In this study inhibitors of DAH7P synthase were prepared which were designed to fit into the binding sites of both PEP and E4P substrates simultaneously. Inhibitors, known to target the PEP binding site, were extended using a C4 linker to include an appropriately placed phosphate group in order to access the phosphate-binding site of E4P. A small increase in inhibition was observed with this modification, and the inhibition results have been rationalised by induced-fit docking.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 17, 1 September 2011, Pages 5092-5097
نویسندگان
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