Abstract
Several important areas of interest intersect in a class of peptides characterized by their highly cationic and partly hydrophobic structure. These molecules have been called cell-penetrating peptides (CPPs) because they possess the ability to translocate across cell membranes. This ability makes these peptides attractive candidates for delivery of therapeutic compounds, especially to the interior of cells. Compounds with characteristics similar to CPPs and that, in addition, have antimicrobial properties are being investigated as antibiotics with a reduced risk of causing resistance. These CPP-like membrane-acting antimicrobial peptides (MAMPs) are α-helical amphipathic peptides that interact with and perturb cell membranes to produce their antimicrobial effects. One source of MAMPs is spider venom. Because these compounds are toxic to insects, they also show promise for development as biological agents for control of insecticide-resistant agricultural pests. Spider venom is a potential source of novel insect-specific peptide toxins. One example is the small amphipathic α-helical peptide lycotoxin-1 (Lyt-1 or LCTX) from the wolf spider (Lycosa carolinensis). One side of the α-helix has mostly hydrophilic and the other mainly hydrophobic amino acid residues. The positive charge of the hydrophilic side interacts with negatively charged prokaryotic membranes and the hydrophobic side associates with the membrane lipid bilayer to permeabilize it. Because the surface of the exoskeleton, or cuticle, of an insect is highly hydrophobic, to repel water and dirt, it would be expected that amphipathic compounds could permeabilize it. Mutagenized lycotoxin 1 peptides were produced and expressed in yeast cultures that were fed to fall armyworm (Spodoptera frugiperda) larvae to identify the most lethal mutants. Transgenic expression of spider venom toxins such as lycotoxin-1 in plants could provide durable insect resistance.
Highlights
The cell membrane is the barrier that protects living cells from the surrounding environment, generally allowing the movement of only small molecules into the cell
It was eventually observed that certain peptides had the ability to pass through cell membranes
cell-penetrating peptides (CPPs) are short, water-soluble and partly hydrophobic, and/or polybasic peptides with a net positive charge at physiological pH. Their ability to translocate across cell membranes is attributed to their highly cationic and partly hydrophobic structure
Summary
The cell membrane is the barrier that protects living cells from the surrounding environment, generally allowing the movement of only small molecules into the cell. CPPs are short (less than 35 amino acid residues), water-soluble and partly hydrophobic, and/or polybasic peptides with a net positive charge at physiological pH Their ability to translocate across cell membranes is attributed to their highly cationic and partly hydrophobic structure. Another class of peptides that have similar characteristics to CPPs and that in addition possess antimicrobial properties is being investigated for use as antibiotics that have a reduced risk of causing resistance [2] These CPP-like membrane-acting antimicrobial peptides (MAMPs) are produced by many organisms as a defense against microbial pathogens. Most have amphipathic α-helical structures that interact with and perturb cell membranes to produce their antimicrobial effects [3,4] They target a wide range of bacteria and fungi and these pathogens do not seem to readily develop resistance [5]. The most lethal mutations appeared to increase the ability of the toxin α-helix to interact with insect cell membranes and disrupt the membranes by forming pores [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
