title: First principles investigation of vancomycin and teicoplanin binding to bacterial cell wall termini.
abstract: The recent rise of vancomycin-resistant enterococci (VRE) has given new impetus to the study of the binding between glycopeptide antibiotics and bacterial cell wall termini. Here, we report on an extensive first principles investigation of the binding of vancomycin and teicoplanin with d-Ala-d-Lac (characteristic of VREs) and d-Ala-d-Ala (characteristic of non-VREs). Binding of both antibiotics to d-Ala-d-Ala was found to be stronger by about 3-5 kcal/mol and due primarily to the oxygen-oxygen lone-pair repulsion characteristic of the antibiotic/d-Ala-d-Lac complex. These results are in good agreement with recent experimental findings.
authors.affiliation: Department of Physics, The North Carolina State University, Raleigh, North Carolina 27695-82802, USA.
authors.forename: Jung-Goo
authors.initials: JG
authors.lastname: Lee
authors.forename: Celeste
authors.initials: C
authors.lastname: Sagui
authors.forename: Christopher
authors.initials: C
authors.lastname: Roland
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism*; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D017334:Teicoplanin / Q000378:metabolism* / Q000494:pharmacology; D013816:Thermodynamics; D014640:Vancomycin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D007773:Lactates; C078877:alanyllactate; C002956:alanylalanine; D017334:Teicoplanin; D014640:Vancomycin; D000409:Alanine