Enhanced membrane pore formation by multimeric/oligomeric antimicrobial peptides.
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.
Arnusch
Christopher J
CJ
Department of Chemical Biology and Organic Synthesis, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.
Branderhorst
Hilbert
H
de Kruijff
Ben
B
Liskamp
Rob M J
RM
Breukink
Eefjan
E
Pieters
Roland J
RJ
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
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