5915-64-0Relevant academic research and scientific papers
Modular synthesis of diphospholipid oligosaccharide fragments of the bacterial cell wall and their use to study the mechanism of moenomycin and other antibiotics
Gampe, Christian M.,Tsukamoto, Hirokazu,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
, p. 9771 - 9778 (2012/02/15)
We present a flexible, modular route to GlcNAc-MurNAc-oligosaccharides that can be readily converted into peptidoglycan (PG) fragments to serve as reagents for the study of bacterial enzymes that are targets for antibiotics. Demonstrating the utility of these synthetic PG substrates, we show that the tetrasaccharide substrate lipid IV (3), but not the disaccharide substrate lipid II (2), significantly increases the concentration of moenomycin A required to inhibit a prototypical PG-glycosyltransferase (PGT). These results imply that lipid IV and moenomycin A bind to the same site on the enzyme. We also show the moenomycin A inhibits the formation of elongated polysaccharide product but does not affect length distribution. We conclude that moenomycin A blocks PG-strand initiation rather than elongation or chain termination. Synthetic access to diphospholipid oligosaccharides will enable further studies of bacterial cell wall synthesis with the long-term goal of identifying novel antibiotics.
Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan
Lupoli, Tania J.,Tsukamoto, Hirokazu,Doud, Emma H.,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
, p. 10748 - 10751 (2011/09/13)
The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse d-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical d-amino acids can be introduced into the bacterial cell wall.
GENERAL METHOD OF STEREOSPECIFIC SYNTHESIS OF NATURAL POLYPRENOLS. SYNTHESIS OF BETULAPRENOL-6, -7, -8, AND -9
Sato, Kikumasa,Miyamoto, Osamu,Inoue, Seiichi,Furusawa, Fumio,Matsuhasi, Yasusuke
, p. 1105 - 1108 (2007/10/02)
A stereoselective synthesis of (Z,Z,Z)-12-benzyloxy-1-chloro-2,6,10-trimethyldodeca-2,6,10-triene was achieved starting from (Z,Z)-farnesol.All the components of betulaprenols were synthesized using the C15 block 3 and its lower homologue (C10 block) as t
SYNTHESIS OF (2Z,6Z,10Z,14E,18E)-FARNESYLFARNESOL
Moiseenkov, Alexander M.,Polunin, Evgeni V.,Semenovsky, Alexei V.
, p. 3309 - 3312 (2007/10/02)
Nine-step synthesis of the title triterpenol from (E,E)-farnesol using a two-stage cis-C5-homologation procedure is described.
