The vancomycin group antibiotics are currently receiving much attention throughout the world because of their activity against methicillin-resistant staphlococci and other Gram positive microorganisms. These antibiotics are glycopeptides having unusual structures; their antimicrobial activity is due to their unique ability to complex with peptide constituents of bacterial cell walls. The goal of this project is to characterize the binding process on a structural level, identifying the sites of hydrogen-bonding and other interactions between the antibiotics and the peptides and establishing the basis for the high structural and stereochemical specificities that are observed. As a prelude to the binding studies, a careful evaluation will be made of the conformation of vancomycin where it appears very likely that errors exist in the work of others. The binding interactions will be probed by UV difference spectra and by high field NMR, first with simple peptides and then with more complicated arrays including peptidoglycans, to search for possible cooperative interactions. Attention will be given to the specific sites of the antibiotic-peptide interactions. The structures of antibiotics will be modified on the basis of results derived from these studies. It is hoped that, through creation of additional sites of hydrogen-bonding between the antibiotics and the cell wall peptides and by other structural alterations, substances can be prepared that have significantly improved antibiotic activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM023593-09
Application #
3271763
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1977-02-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
9
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Arts and Sciences
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Harris, C M; Kopecka, H; Harris, T M (1985) The stabilization of vancomycin by peptidoglycan analogs. J Antibiot (Tokyo) 38:51-7