Antibiotic resistance has become a major problem in hospitals and in the community and we need new antibiotics to forestall a public health crisis. The research proposed here is directed towards understanding the molecular basis by which some glycopeptide derivatives overcome antibiotic resistance and towards understanding the mechanism of action of moenomycin, a potent antibiotic that inhibits a major but underexploited antibacterial target, the transglycosyalses. Efficient chemoenzymatic and synthetic routes to glycolipid derivatives and moenomycin analogues are proposed, and the compounds that are made will be tested in both cell-based and enzymological assays in order to provide insight into structure-activity relationships. We also propose experiments to understand the mechanistic basis for how glycopeptide analogues overcome vanA and vanB resistance. A better understanding of the mechanisms by which resistance can be overcome, combined with information on how activity varies as a function of structure, could lead to the development of new antibiotics that overcome common forms of antibiotic resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM066174-08
Application #
7644827
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2002-07-01
Project End
2010-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
8
Fiscal Year
2009
Total Cost
$532,824
Indirect Cost
Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
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