The amphipathic styles are crucial for the biological properties of AMPs. Changing the amphipathic design by rearrangement of hydrophilic and hydrophobic components or applying other chemical modifications can significantly affect the interaction between AMPs and targeted membranes.

Abstract

Amphipathicity is a critical characteristic of helical antimicrobial peptides (AMPs). The hydrophilic region, primarily composed of cationic residues, plays a pivotal role in the initial binding to negatively charged components on bacterial membranes through electrostatic interactions. Subsequently, the hydrophobic region interacts with hydrophobic components, inducing membrane perturbation, ultimately leading to cell death, or inhibiting intracellular function. Due to the extensive diversity of natural and synthetic AMPs with regard to the design of amphipathicity, it is complicated to study the structure-activity relationships. Therefore, this work aims to categorize the common amphipathic design and investigate their impact on the biological properties of AMPs. Besides, the connection between current structural modification approaches and amphipathic styles was also discussed.