Membrane Active Peptides and Their Biophysical Characterization

Abstract

In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

“…Accordingly, they can be: (1) cationic, which comprises peptides with highly positive charges at physiological pH; (2) amphipathic, that contains both polar (hydrophilic) and nonpolar (hydrophobic) regions of amino acids; and (3) hydrophobic, the less studied class, which are CPPs mainly containing nonpolar residues, resulting in a low net charge. Naturally occurring proteins and peptides are the principal sources of CPPs [105,106], however, to optimize the peptides' properties, fully engineered peptides have been designed, based on computational modeling [107].…”

Computational identification of self-inhibitory peptides from white spot syndrome virus envelope protein VP28

“…Identification of its antimicrobial activity may support this point, this peptide possessed an amphiphilic structure, the obvious characteristic of an antimicrobial peptide. Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity either by pore formation or through nonspecific membrane permeabilization (Lee et al, 2016;Avci et al, 2018). Similarly, this peptide functioning as an antimicrobial peptide also may bind to the similar proteins of used bacteria, which could be concluded from the docking results of the peptide and these proteins (Fig.…”

Biofunctionalization of Natural Fiber-Reinforced Biocomposites for Biomedical Applications

“…Most AMPs reported to date can be characterized as one of the following four types, based on their secondary structures: β-sheet, α-helix, extended and loop. Even though the β-sheet structure is the most common, it is only formed when the peptide comes in contact with a membrane [149][150][151][152][153]. In the case of natural origin AMPs, they can be isolated from both prokaryotes and eukaryotes.…”

“…Most AMPs are produced by specific cells, at all times; however, there are those whose production is inducible. Still, they are quickly mobilized after microbial infection and act rapidly to neutralize a broad range of microbes (Figure 3) [149,150,[153][154][155][156]. To date, hundreds of AMPs have been identified and their importance in the innate immune system explored.…”