LEADS THAT TARGET P. FALCIPARUM ENR

Project: Research project

Project Details

Description

Project 1 will focus on the development of lead compounds that target the enoyl-ACP
reductase from Plasmodium falciparum. This will be done by developing structure-activity
relationships (SAR) for novel series of compounds discovered from high throughput screens
(HTS) against the purified recombinant enzyme. The synthesis of structural analogs of hits
from the HTS and testing by in vitro enyzme assays will be carried out in collaboration
between Sacchettini's lab at Texas A&M University and Dr. Garcia-Bustos's lab at
GlaxoSmithKline (GSK). As an integral part of this process, the Sacchettini lab will focus on
obtaining the crystal structures of PfENR in complex with the most promising lead
compounds. A greater understanding of the detailed interactions between the enzyme and the
inhibitor, including specific contacts between functional groups and amino acid side chains,
and the conformation of the bound inhibitor, will be derived from the structural analyses and
will guide the synthetic chemists. The Garcia-Bustos lab together with other colleagues at
GSK will focus on chemical synthesis and medicinal chemistry of the most promising
compounds to ensure good pharmacokinetic profiles. GSK will be responsible for a thorough
work-up of PK, PD, ADME and toxicity for lead compounds and with their vast experience of
developing new pharmaceuticals, this will guarantee the greatest chance of success in the
overall aims of the Program Project.
StatusFinished
Effective start/end date4/1/045/31/09

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)