title: Locations of the hydrophobic side chains of lipoglycopeptides bound to the peptidoglycan of Staphylococcus aureus.
abstract: Glycopeptides whose aminosugars have been modified by attachment of hydrophobic side chains are frequently active against vancomycin-resistant microorganisms. We have compared the conformations of six such fluorinated glycopeptides (with side chains of varying length) complexed to cell walls labeled with d-[1-(13)C]alanine, [1-(13)C]glycine, and l-[ε-(15)N]lysine in whole cells of Staphylococcus aureus. The internuclear distances from (19)F of the bound drug to the (13)C and (15)N labels of the peptidoglycan, and to the natural abundance (31)P of lipid membranes and teichoic acids, were determined by rotational-echo double resonance NMR. The drugs did not dimerize, and their side chains did not form membrane anchors but instead became essential parts of secondary binding to pentaglycyl bridge segments of the cell-wall peptidoglycan.
authors.affiliation: Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798, United States.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kelly S E
authors.initials: KS
authors.lastname: Tanaka
authors.forename: Evelyne
authors.initials: E
authors.lastname: Dietrich
authors.forename: Adel
authors.initials: A
authors.lastname: Rafai Far
authors.forename: Jacob
authors.initials: J
authors.lastname: Schaefer
mesh_terms: D000409:Alanine / Q000235:genetics; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D005998:Glycine / Q000235:genetics; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010457:Peptidoglycan / Q000737:chemistry* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D006020:Glycopeptides; D010457:Peptidoglycan; D008239:Lysine; D000409:Alanine; D005998:Glycine