Membrane disrupting antimicrobial peptide dendrimers with multiple amino termini

Antimicrobial peptide dendrimer H1 Leu(8)(Lys-Leu)(4)(Lys-Phe)(2)Lys-LysNH(2) (Lys = branching lysine) was identified by screening a 6750-membered combinatorial library by the bead-diffusion assay. Sequence variations also revealed dendrimer bH1 Leu(8)(Dap-Leu)(4)(Dap-Phe)(2)Dap-LysNH(2) (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 mu g mL(-1) on Bacillus subtilis and Escherichia coli) but low hemolytic activity (MHC = 310 mu g mL(-1) respectively >2000 mu g mL(-1)).