title: Chimerization of lactoferricin and lactoferrampin peptides strongly potentiates the killing activity against Candida albicans.
abstract: Bovine lactoferrin harbors 2 antimicrobial sequences (LFcin and LFampin), situated in close proximity in the N1-domain. To mimic their semi parallel configuration we have synthesized a chimeric peptide (LFchimera) in which these sequences are linked in a head-to-head fashion to the α- and ε-amino group, respectively, of a single lysine. In line with previously described bactericidal effects, this peptide was also a stronger candidacidal agent than the antimicrobial peptides LFcin17-30 and LFampin265-284, or a combination of these 2. Conditions that strongly reduced the candidacidal activities of LFcin17-30 and LFampin265-284, such as high ionic strength and energy depletion, had little influence on the activity of LFchimera. Freeze-fracture electron microscopy showed that LFchimera severely affected the membrane morphology, resulting in disintegration of the membrane bilayer and in an efflux of small and high molecular weight molecules such as ATP and proteins. The differential effects displayed by the chimeric peptide and a mixture of its constituent peptides clearly demonstrate the synergistic effect of linking these peptides in a fashion that allows a similar spatial arrangement as in the parent protein, suggesting that in bovine lactoferrrin the corresponding fragments act in concert in its candidacidal activity.
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, NL-1081AL, Amsterdam, The Netherlands. j.bolscher@acta.nl
authors.forename: Jan
authors.initials: J
authors.lastname: Bolscher
authors.forename: Kamran
authors.initials: K
authors.lastname: Nazmi
authors.forename: Jan
authors.initials: J
authors.lastname: van Marle
authors.forename: Wim
authors.initials: W
authors.lastname: van 't Hof
authors.forename: Enno
authors.initials: E
authors.lastname: Veerman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005456:Fluorescent Dyes / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010539:Permeability; D011419:Propidium / Q000378:metabolism; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D005456:Fluorescent Dyes; D005656:Fungal Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C502040:lactoferrampin; C082171:lactoferricin B; D011419:Propidium; D007781:Lactoferrin