Crown ether modified peptides: Length and crown ring size impact on membrane interactions.
Pierre-Alexandre Paquet-Côté1, Jean-Philippe Paradis1, Michèle Auger2
1Département de Chimie and PROTEO, Université Laval, 1045 avenue de la Médecine, Québec G1V 0A6, Canada.
Biochimica Et Biophysica Acta. Biomembranes
|March 11, 2020
Summary
Researchers explored modified antimicrobial peptides (AMPs) with crown ethers, finding that longer peptides and specific ring sizes enhance cell membrane permeabilization, aiding in designing more effective AMPs.
Area of Science:
- Biochemistry
- Biophysics
- Medicinal Chemistry
Background:
- Antimicrobial peptides (AMPs) are promising antibiotic alternatives.
- Developing potent and selective AMPs is challenging due to complex structure-activity relationships.
Purpose of the Study:
- Investigate the impact of structural modifications on AMPs bearing crown ethers.
- Determine how peptide length and crown ether ring size affect secondary structure and membrane permeabilization.
Main Methods:
- Circular dichroism spectroscopy to analyze peptide secondary structures.
- Permeabilization assays using model membranes (phosphatidylcholine, phosphatidylglycerol) and red blood cells.
Main Results:
- Peptide length and crown ether size influenced peptide conformation, though no clear trend emerged.
- Increasing peptide length from 13 to 16 residues enhanced membrane permeabilization.
- Shortened analogs (12 residues) showed increased activity upon crown ether-bearing amino acid removal.
- Larger crown ether ring sizes correlated with higher hemolytic activity.
Conclusions:
- Structural modifications, specifically peptide length and crown ether size, significantly impact AMP activity.
- Results provide insights for designing novel, more selective antimicrobial peptides.
Related Concept Videos
02:36Crown Ethers
5.9K
Crown ethers are cyclic polyethers that contain multiple oxygen atoms, usually arranged in a regular pattern. The first crown ether was synthesized by Charles Pederson while working at DuPont in 1967. For this work, Pedersen was co-awarded the 1987 Nobel Prize in Chemistry. Crown ethers are named using the formula x-crown-y, where x is the total number of atoms in the ring and y is the number of ether oxygen atoms. The term 'crown' refers to the crown-like shape that these ether molecules...
5.9K
00:59Mechanisms of Membrane Domain Formation
3.7K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
Another mechanism for membrane domain formation involves membrane proteins interacting with...
3.7K
01:18Membrane Domains
6.9K
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
6.9K
01:32Lipids as Anchors
7.0K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
7.0K
01:23Membrane Fluidity
171.5K
Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.
171.5K
01:26Membrane Fluidity
14.2K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
14.2K