Effects of chain length and hydrophobicity/charge ratio of AMP on its antimicrobial activity

Using two series of de novo designed antimicrobial peptides,we studied the effects of peptide length and hydrophobicity/charge(H/C) ratio on the antimicrobial activities.For these peptides,a correlation was established between their antimicrobial efficacy and the leakage,aggregation,and fusion activities on artificial membrane.The results showed that peptides with an H/C ratio of 1.3,and a length of about half of the membrane thickness caused most potent membrane leakage,and negligible membrane aggregation and fusion.In addition,such peptide also exhibited the highest antimicrobial activity.Analysis of the hydrophobic and electrostatic interactions showed that the strength,the order and the position of these interactions determined the activities of the peptides on the artificial membrane and thus the antimicrobial efficacy.Further analyses on the tilt angle of the peptides on the membrane surface indicated that the peptides distorted the membrane in a dynamic mode,instead of being fixed in the membrane at a constant angle.