TY - JOUR
T1 - Pseudilins
T2 - Halogenated, allosteric inhibitors of the non-mevalonate pathway enzyme IspD
AU - Kunfermann, Andrea
AU - Witschel, Matthias
AU - Illarionov, Boris
AU - Martin, René
AU - Rottmann, Matthias
AU - Höffken, H. Wolfgang
AU - Seet, Michael
AU - Eisenreich, Wolfgang
AU - Knölker, Hans Joachim
AU - Fischer, Markus
AU - Bacher, Adelbert
AU - Groll, Michael
AU - Diederich, François
PY - 2014/2/17
Y1 - 2014/2/17
N2 - The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis have been identified as attractive targets with novel modes of action for the development of herbicides for crop protection and agents against infectious diseases. This pathway is present in many pathogenic organisms and plants, but absent in mammals. By using high-throughput screening, we identified highly halogenated marine natural products, the pseudilins, to be inhibitors of the third enzyme, IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis thaliana and Plasmodium vivax was determined in photometric and NMR-based assays.
AB - The enzymes of the non-mevalonate pathway for isoprenoid biosynthesis have been identified as attractive targets with novel modes of action for the development of herbicides for crop protection and agents against infectious diseases. This pathway is present in many pathogenic organisms and plants, but absent in mammals. By using high-throughput screening, we identified highly halogenated marine natural products, the pseudilins, to be inhibitors of the third enzyme, IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis thaliana and Plasmodium vivax was determined in photometric and NMR-based assays.
KW - allosteric inhibition
KW - antiinfectives
KW - drug discovery
KW - halogen bonding
KW - herbicides
KW - pseudilins
UR - http://www.scopus.com/inward/record.url?scp=84893869668&partnerID=8YFLogxK
U2 - 10.1002/anie.201309557
DO - 10.1002/anie.201309557
M3 - Article
C2 - 24446431
AN - SCOPUS:84893869668
SN - 1433-7851
VL - 53
SP - 2235
EP - 2239
JO - Angewandte Chemie International Edition in English
JF - Angewandte Chemie International Edition in English
IS - 8
ER -
