SANS study of membrane binding of pH-responsive cationic AMPs containing aspartic acids

Histidine-rich natural antimicrobial peptides (AMPs) such as Piscidins from fish and Hepcidin from human liver have demonstrated enhanced antibacterial potency at acidic pH than at neutral pH. Inspired by the facilitating effects of net cationic charges on membrane-activity, pH-responsive aspartic acid (D) has been introduced into the rational design of new AMPs in this work. GIIKKIIDDIIKKI (denoted as 2D) and G(IIKD)3I (denoted as 3D) show very different antimicrobial actions at the acidic pH from those at the physiological pH. Our broad aim in this work is to examine how variations in amphipathic characters associated with aspartic acid in the AMPs based on IIKK repeats affect their peptide self-assembly and pH-responsiveness, and their subsequent ability to attack model lipid bilayers created from model small unilamellar vesicles that facilitate SANS studies.