Accession Number : ADA510174


Title :   Institute for Advanced Pharmaceutical Sciences: Molecular Targets and Drug Screens to Combat Bioterrorism


Descriptive Note : Final rept. 1 Jul 2007-30 Nov 2008


Corporate Author : ILLINOIS UNIV AT CHICAGO


Personal Author(s) : Bauman, Jerry L.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA510174


Report Date : DEC 2008


Pagination or Media Count : 153


Abstract : Anthrax continues to be a major threat to our national security and economy. We used multiple approaches for the development of novel therapeutics. (1) We engineered three isogenic mutant E.coli strains to be used for HTS screening for selective and specific inhibitors of anthrax protein synthesis. (2) We developed 2 assays for quantitation of peptide self-assembly and showed that ACDs inhibit specific aggregation pathways. (3) We demonstrated that inhibitors of FabI exhibit broad spectrum of activity against a variety of pathogens, and started to develop additional enzymatic targets in the fatty acid biosynthetic pathway. (4) We developed synthetic schemes for series of Antibiotic A-33853 derivatives and improved the potency of the original A-33853 two-fold against B. anthracis, and demonstrated that these derivatives are effective against wide spectrum of pathogens, including L. donovani. (5) We have developed automated MIC assay that can be used to screen up to 100K compounds/day against bacteria, and identified three structural classes as potential lead scaffolds for future medicinal chemistry improvement.


Descriptors :   *BACILLUS ANTHRACIS , *NATIONAL SECURITY , *BIOTERRORISM , *THREATS , ANTHRAX , PATHOGENIC MICROORGANISMS , BIOSYNTHESIS , INHIBITORS , MUTATIONS , PROTEINS , ECONOMIC IMPACT , THERAPY


Subject Categories : MEDICINE AND MEDICAL RESEARCH
      PHARMACOLOGY
      MICROBIOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE