Lāce I, Cotroneo ER, Hesselbarth N, Simeth NA
Journal of Peptide Science
J Pept Sci. 2022 Dec 7:e3466.
Membranes consisting of phospholipid bilayers are an essential constituent of eukaryotic cells and their compartments. The alteration of their composition, structure and morphology plays an important role in modulating physiological processes, such as transport of molecules, cell migration, or signaling, but it can also lead to lethal effects. The three main classes of membrane active peptides that are responsible for inducing such alterations are cell penetrating peptides (CPPs), antimicrobial peptides (AMPs) and fusion peptides (FPs). These peptides are able to interact with lipid bilayers in highly specific and tightly regulated manners. They can either penetrate the membrane, inducing non-destructive, transient alterations, or disrupt, permeabilize or translocate through it, or induce membrane fusion by generating attractive forces between two bilayers. Due to these properties membrane active peptides have attracted the attention of the pharmaceutical industry, and naturally occurring bioactive structures have been used as a platform for synthetic modification and the development of artificial analogues with optimized therapeutic properties to transport biologically active cargos or serve as novel antimicrobial agents. In this review, we focus on synthetic membrane interacting peptides with bioactivity comparable to their natural counterparts and describe their mechanism of action.