title: Enhanced membrane pore formation by multimeric/oligomeric antimicrobial peptides.
abstract: The pore-forming antibacterial peptide magainin 2 was made divalent, tetravalent, and octavalent via a copper(I)-mediated 1-3 dipolar cycloaddition reaction ("click" chemistry). This series of pore-forming compounds was tested in vitro for their ability to form pores in large unilamillar vesicles (LUVs). A large increase in the pore-forming capability was especially observed with the tetravalent and octavalent magainin compounds in the LUVs consisting of DOPC, and the octavalent magainin compound showed a marked increase with the DOPC/DOPG LUVs. Activity was observed in the low nanomolar range for these compounds.
authors.affiliation: Department of Chemical Biology and Organic Synthesis, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Arnusch
authors.forename: Hilbert
authors.initials: H
authors.lastname: Branderhorst
authors.forename: Ben
authors.initials: B
authors.lastname: de Kruijff
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
authors.forename: Eefjan
authors.initials: E
authors.lastname: Breukink
authors.forename: Roland J
authors.initials: RJ
authors.lastname: Pieters
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability; D005452:Fluoresceins / Q000737:chemistry; D054806:Magainins / Q000138:chemical synthesis / Q000737:chemistry*; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D054806:Magainins; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D053835:Unilamellar Liposomes; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; C017251:1,2-oleoylphosphatidylcholine