Abstract

CORE C: The objectives of the core are to facilitate the discovery and development of inhibitors of virulence factor proteins from biowarfare pathogens that are targeted by the projects. The Core will provide a small molecule high throughput screening (HTS) facility for screening proteins. These inhibitors will be verified and transferred for NMR-based optimization strategies to enhance their selectivity and affinity amongst other properties. Core chemists, in collaboration, will develop designs for focused analog libraries based on NMR data.
The specific aims are:
Aim 1. Provide small molecule high throughput (HTS) screening of virulence factors. These factors include CrmA and Spi1, a detoxified mutant of BoNT/C, Yop J, YopH, and new virulence factors.
Aim 2. Provide a chemical synthesis lab and synthetic assistance for the NMR-based optimization of small molecules and for resynthesis of lead compounds.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI055789-01A1
Application #
6800916
Study Section
Special Emphasis Panel (ZAI1-QV-M (J1))
Project Start
2004-04-01
Project End
2009-03-31
Budget Start
2004-07-05
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$784,774
Indirect Cost

  Institution

Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Aleshin, Alexander E; DiScipio, Richard G; Stec, Boguslaw et al. (2012) Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex. J Biol Chem 287:19642-52
Low, Lieh Yoon; Yang, Chen; Perego, Marta et al. (2011) Role of net charge on catalytic domain and influence of cell wall binding domain on bactericidal activity, specificity, and host range of phage lysins. J Biol Chem 286:34391-403
Shiryaev, Sergey A; Chernov, Andrei V; Shiryaeva, Tatiana N et al. (2011) The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase. Arch Virol 156:313-8
Stranzl, Gudrun R; Santelli, Eugenio; Bankston, Laurie A et al. (2011) Structural insights into inhibition of Bacillus anthracis sporulation by a novel class of non-heme globin sensor domains. J Biol Chem 286:8448-58
Zhai, Dayong; Yu, Eric; Jin, Chaofang et al. (2010) Vaccinia virus protein F1L is a caspase-9 inhibitor. J Biol Chem 285:5569-80
Zhao, Li-Chun; Yang, Bo; Wang, Rengang et al. (2010) Type C botulinum toxin causes degeneration of motoneurons in vivo. Neuroreport 21:14-18
Shiryaev, Sergey A; Radichev, Ilian A; Ratnikov, Boris I et al. (2010) Isolation and characterization of selective and potent human Fab inhibitors directed to the active-site region of the two-component NS2B-NS3 proteinase of West Nile virus. Biochem J 427:369-76
Remacle, Albert G; Gawlik, Katarzyna; Golubkov, Vladislav S et al. (2010) Selective and potent furin inhibitors protect cells from anthrax without significant toxicity. Int J Biochem Cell Biol 42:987-95
Chan, Siew Leong; Mukasa, Takashi; Santelli, Eugenio et al. (2010) The crystal structure of a TIR domain from Arabidopsis thaliana reveals a conserved helical region unique to plants. Protein Sci 19:155-61
Shiryaev, Sergey A; Strongin, Alex Y (2010) Structural and functional parameters of the flaviviral protease: a promising antiviral drug target. Future Virol 5:593-606

Showing the most recent 10 out of 48 publications