کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1375422 | 981938 | 2008 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis and analysis of a fluorinated product analogue as an inhibitor for 1-deoxy-d-xylulose 5-phosphate reductoisomerase
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
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چکیده انگلیسی
1-Deoxy-d-xylulose 5-phosphate (DXP) reductoisomerase (DXR) is an NADPH-dependent enzyme catalyzing the rearrangement and reduction of DXP to methyl-d-erythritol 4-phosphate (MEP). Two mechanisms for this enzymatic reaction have been proposed, involving either an α-ketol rearrangement or a retroaldol/aldol rearrangement. In this study, a fluorinated product analogue, FCH2-MEP, was synthesized as a possible mechanism-based inactivator for DXR if the retroaldol/aldol mechanism is operative. FCH2-MEP was found to be a weak competitive inhibitor, and thus was unable to discriminate between the mechanisms. This result is due to the inability of the targeted enzyme, DXR, to oxidize FCH2-MEP to the aldehyde intermediate that is common to both mechanisms. While FCH2-MEP failed to act as a mechanism-based inactivator, the insight gained from this study will assist in the future design of inhibitors of DXR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 10, 15 May 2008, Pages 3090-3094
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 18, Issue 10, 15 May 2008, Pages 3090-3094
نویسندگان
Jeffrey W. Munos, Xiaotao Pu, Hung-wen Liu,