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Membrane disrupting antimicrobial peptide dendrimers with multiple amino termini†
Michaela Stach,Noélie Maillard,Rameshwar U. Kadam,David Kalbermatter,Marcel Meury,Malcolm G. P. Page,Dimitrios Fotiadis,Tamis Darbre,Jean-Louis Reymond
MedChemComm Pub Date : 11/23/2011 00:00:00 , DOI:10.1039/C1MD00272D
Abstract

Antimicrobial peptide dendrimer H1 Leu8(Lys-Leu)4(Lys-Phe)2Lys-LysNH2 (Lys = branching lysine) was identified by screening a 6750-membered combinatorial library by the bead-diffusion assay. Sequence variations also revealed dendrimer bH1 Leu8(Dap-Leu)4(Dap-Phe)2Dap-LysNH2 (Dap = branching 2,3-diaminopropanoic acid) as a more potent analog. H1 and bH1 showed good antimicrobial activities mediated by membrane disruption (MIC = 2–4 μg mL−1 on Bacillus subtilis and Escherichia coli) but low hemolytic activity (MHC = 310 μg mL−1 respectively >2000 μg mL−1).

Graphical abstract: Membrane disrupting antimicrobial peptide dendrimers with multiple amino termini
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