title: Antibacterial and immunostimulatory properties of chemotactic N-formyl peptide conjugates of ampicillin and amoxicillin.
abstract: N-Formyl dipeptide conjugates of ampicillin and amoxicillin related to the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine were synthesized and assessed for antibacterial activity and affinity for the chemotactic peptide receptor of differentiated human promyelocytic leukemia (HL-60) cells. The conjugates and parent beta-lactam antibiotics showed similar antibacterial activities against Escherichia coli and Staphylococcus aureus. The affinity of each conjugate for the chemotactic peptide receptor was determined in a competitive binding assay, using 3H-labeled N-formyl-L-methionyl-L-leucyl-L-phenylalanine. All conjugates bound to the receptor, but with affinities ranging from 1/3 to 1/100 that of the tritiated substrate. There was good correlation between receptor affinity and stimulation of chemotaxis. The peptide-antibiotic conjugates also stimulated the oxidative metabolism of the HL-60 cells by inducing the production of superoxide and hydrogen peroxide as determined by Luminol- and Lucigenin-enhanced chemiluminescence. These conjugates, based on N-formyl-L-methionyl-L-leucyl-L-phenylalanine, thus combine both potent antibacterial and immunostimulatory properties within the same molecule.
authors.affiliation: Department of Pharmaceutical Sciences, The University, Nottingham, United Kingdom.
authors.forename: B W
authors.initials: BW
authors.lastname: Bycroft
authors.forename: P M
authors.initials: PM
authors.lastname: Lockey
authors.forename: A
authors.initials: A
authors.lastname: Penrose
authors.forename: R J
authors.initials: RJ
authors.lastname: Grout
authors.forename: P
authors.initials: P
authors.lastname: Williams
mesh_terms: D000276:Adjuvants, Immunologic; D000658:Amoxicillin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000667:Ampicillin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008163:Luminescent Measurements; D008826:Microbial Sensitivity Tests; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000667:Ampicillin; D000658:Amoxicillin; D006861:Hydrogen Peroxide; D004121:Dimethyl Sulfoxide