Prokaryotic selectivity and LPS-neutralizing activity of short antimicrobial peptides designed from the human antimicrobial peptide LL-37

► The proper hydrophobicity of antimicrobial peptides is crucial to exert the amalgamated property of LPS-neutralizing activity and prokaryotic selectivity. ► Analog a4-W2 showed more improved prokaryotic selectivity compared to LL-37. ► Analog a4-W2 displayed LPS-neutralizing activity comparable to that of LL-37. ► The effective site of Trp-substitution for high LPS-neutralizing activity of α-helical antimicrobial peptides is the amphipathic interface in the α-helical wheel projection.