MEDI 148 |
| Suzanne Walker, Department of Chemistry, Department of Chemistry, Princeton University, 169 Frick Laboratory, Washington Road & Williams Street, Princeton, NJ 08540 |
| The major constituent of the bacterial cell wall is peptidoglycan, a mesh-like polymer comprised of carbohydrate chains held together by peptide crosslinks. The peptidoglycan layers surrounding bacterial cells strengthen bacterial cell membranes and keep the cells from lysing under high internal osmotic pressures. An intact peptidoglycan layer is necessary for survival, which means that compounds that interfere with peptidoglycan biosynthesis have antibiotic activity. Because resistance to existing antibiotics has become a serious problem, there is considerable interest in knowing more about how peptidoglycan is made and how the biosynthetic pathway can be inhibited. The enzymes involved in the late steps of peptidoglycan biosynthesis have been difficult to study, largely because their substrates are not readily available from natural sources. We have been developing chemical approaches to study some of the late stage enzymes of peptidoglycan biosynthesis. We will talk about the tools we have developed and what we have learned about two of the enzymes, MurG and PBP1b. We will also show how substrate analogues and direct enzyme assays can be used to probe the mechanism of action of putative substrate-binding antibiotics. The antibiotic we will focus on is ramoplanin, a compound that is currently in Phase III clinical trials. We have recently disproven the proposed mechanism of action for this compound and have suggested an alternative that is now being tested. |
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ACS Award in Industrial Chemistry Symposium
8:45 AM-12:00 PM, Monday, March 24, 2003 Convention Center -- La Nourvelle Ballroom C, Oral
Division of Medicinal Chemistry |