Gram-negative bacteria are a major cause of natural outbreaks of disease and feature prominently in the biological arsenals of rogue nations. Compounding this problem is the fact that bacteria are becoming increasingly resistant to current therapeutics, reducing the ability of today's antibiotics to treat the victims of natural outbreaks or attacks from engineered pathogens. We propose to target LpxK, an essential kinase involved in the biosynthetic pathway of Lipid A, a major constituent of the gram-negative outer membrane, as a means to develop novel compounds that can prevent or treat bacterial infections with gram-negative bacteria. Innovative surface-based assays will be used to screen compounds against LpxK. Once promising lead compounds are identified, we will perform iterative rounds of medicinal chemistry, optimizing their ability to block enzymatic modification, their efficacy on a variety of bacteria and their pharmacokinetic properties.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI056485-01
Application #
6689351
Study Section
Special Emphasis Panel (ZAI1-ALR-M (M4))
Program Officer
Schaefer, Michael R
Project Start
2003-08-15
Project End
2005-07-31
Budget Start
2003-08-15
Budget End
2004-07-31
Support Year
1
Fiscal Year
2003
Total Cost
$982,000
Indirect Cost
Name
Surface Logix, Inc.
Department
Type
DUNS #
945587223
City
Brighton
State
MA
Country
United States
Zip Code
02135