Artificial peptides to induce membrane denaturation and disruption and modulate membrane composition and fusion

• Published in: Journal of peptide science 2023-05, Vol.29 (5), p.e3466-n/a
• Main Authors: Lāce, Ilze, Cotroneo, Elena R., Hesselbarth, Nils, Simeth, Nadja A.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Peptides; Biological activity; Cell Membrane - chemistry; Cell migration; cell penetrating peptides; Cell-Penetrating Peptides - chemistry; Composition; Cytology; Denaturation; Lethal effects; Lipid bilayers; Lipid Bilayers - analysis; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; membrane; Membrane composition; Membrane fusion; Membranes; Peptides; Pharmaceutical industry; Phospholipids; SNAREs
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.3466

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 nondestructive, transient alterations, or disrupt, permeabilize, or translocate through it, or induce membrane fusion by generating attractive forces between two bilayers. Because of 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 analogs 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 with their natural counterparts and describe their mechanism of action. The three main classes of membrane‐active peptides are cell‐penetrating peptides, antimicrobial peptides, and fusion peptides. These peptides are able to interact with lipid bilayers in highly specific and tightly regulated manners. This review focuses on synthetic membrane interacting peptides with bioactivity comparable with their natural counterparts, describing their mechanism of action.