Substrate analogues to study cell-wall biosynthesis and its inhibition.
It has been known for more than 30 years that Lipid II is an intermediate in peptidoglycan synthesis. Recently, it has become apparent that it is also an important target of numerous antibiotics, including the glycopeptides, the lantibiotics and ramoplanin. It is also utilized by sortases in the construction of Gram-positive cell walls. Recent progress has been made in the synthesis of peptidoglycan intermediates that can be used to study enzymes which make peptidoglycan. These intermediates also enable studies to probe the mechanism of action of a variety of substrate-binding antibiotics.
Lazar
Kristi
K
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA. klazar@princeton.edu
Walker
Suzanne
S
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D009005:Monosaccharides / Q000096:biosynthesis / Q000737:chemistry*; D009842:Oligopeptides / Q000096:biosynthesis / Q000737:chemistry*; D010457:Peptidoglycan / Q000096:biosynthesis*; D011485:Protein Binding; D013379:Substrate Specificity; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D008055:Lipids; D009005:Monosaccharides; D009842:Oligopeptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C438940:lipid I; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; D016695:Glycosyltransferases