Synthesis of substrate analogues for the methylerythritol phosphate pathway

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Title Synthesis of substrate analogues for the methylerythritol phosphate pathway
Publication Type dissertation
School or College College of Science
Department Chemistry
Author Krasutsky, Sergiy G.
Date 2011-08
Description Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), precursors for the biosynthesis of terpenoids, can be formed either by the mevalonate or methylerythritol phosphate pathway. The methylerythritol phosphate (MEP) pathway is not present in humans, therefore the enzymes of the pathway are potential targets for the development of novel antibiotic agents. Five steps, catalyzed by the ispD-H proteins, are required for the enzymatic conversion of MEP to IPP and DMAPP. Analogues for MEP, aminomethylerythritol phosphate (NMEP), methylerythritol thiophosphate (MESP), and thiomethylerythritol phosphate (SMEP) were synthesized and their enzymatic activity for conversion to the cyclic intermediates by the consecutive action of three proteins, ispD, ispE, and ispF, is examined. The last step of the pathway, catalyzed by the ispH, requires elimination of the hydroxyl group from hydroxydimethylallyl diphosphate (HDMAPP), the immediate precursor of IPP and DMAPP. Analogues of HDMAPP, aminodimethylallyl diphosphate (NDMAPP), and thiodimethylallyl diphosphate (SDMAPP) were synthesized as substrates or inhibitors for ispH protein.
Type Text
Publisher University of Utah
Subject Hydroxydimethylallyl diphosphate; MEP; Methylerythritol; Terpenoid
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Rights Management Copyright © Sergiy G. Krasutsky 2011
Format application/pdf
Format Medium application/pdf
Format Extent 4,165,308 bytes
Identifier us-etd3,52152
Source Original housed in Marriott Library Special Collections, QD3.5 2011 .K737
ARK ark:/87278/s6tt55nq
Setname ir_etd
ID 194342
Reference URL https://collections.lib.utah.edu/ark:/87278/s6tt55nq
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