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SUMMARY:Target-based anti-infective discovery
DTSTART:20200129T161500
DTEND:20200129T173000
DTSTAMP:20260408T074218Z
UID:9ae073a7b9c8ad295ed0185761cb417822fdd3a7c30543355c78d7db
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Anna Hirsch. Helmholtz Institute for Pharmaceutical Rese
 arch Saarland\nThe challenges associated with anti-infective drug-discover
 y programmes can be tackled by combining antibacterial screening with seve
 ral established and unprecedented hit-identification strategies in paralle
 l. This approach will be illustrated using two targets: The first is the e
 nzyme DXS  from the methyl erythritol phosphate pathway\,  which is esse
 ntial for pathogens such as Mycobacterium tuberculosis and Plasmodium falc
 iparum for the biosynthesis of the essential isoprenoid precursors\, but a
 bsent in humans. We identified inhibitors with promising in vitro and anti
 -infective activity (M. tuberculosis and P. falciparum) using a number of
   hit-identification strategies\, namely ligand- and structure-based virt
 ual screening\, phage display\, dynamic combinatorial chemistry and de nov
 o fragment-based design.\nThe second target is a vitamin transporter from 
 the energy-coupling factor (ECF) class\, which consist of an energising mo
 dule and a substrate-binding protein (S-component). Different S-components
  can interact with the same energising module. We designed and synthesised
  substrate analogues with high affinity (Kd = 4–660 nM) and confirmed th
 e predicted binding mode. A structure-based virtual screening campaign pro
 vided us with the first allosteric inhibitors of the transporter for folat
 e\, which are not cytotoxic and show promising antibacterial (S. aureus an
 d S. pneumoniae) activity.\n 
LOCATION:BCH 2201 https://plan.epfl.ch/?room==BCH%202201
STATUS:CONFIRMED
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