Abstract
Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides.
Keywords: Amyloid peptides, Anti-microbial peptides, Cell-penetrating peptides, Lipid membrane, Membrane active peptides, Pore-formation.
Current Topics in Medicinal Chemistry
Title:Current Understanding of the Mechanisms by which Membrane-Active Peptides Permeate and Disrupt Model Lipid Membranes
Volume: 16 Issue: 2
Author(s): Delin Sun, Jan Forsman and Clifford E. Woodward
Affiliation:
Keywords: Amyloid peptides, Anti-microbial peptides, Cell-penetrating peptides, Lipid membrane, Membrane active peptides, Pore-formation.
Abstract: Three classes of membrane active peptides (MAPs) are considered in this review: cell penetrating peptides (CPPs); anti-microbial peptides (AMPs), and amyloidal peptides. We summarize both experimental and theoretical results for several representative peptides in these different classes, which highlight commonalities in their interactions with model lipid membranes. While it is clear that no fixed set of mechanisms completely characterize any particular class of MAPs, there is certainly evidence that common mechanisms can be found within and between classes. For example, CPPs appear to undergo rapid translocation across lipid bilayers through small transient pores, which nevertheless appear not to cause persistent damage to membranes. On the other hand, AMPs also show evidence of rapid translocation, but associated with this, is membrane rupture to form large pores, which are subsequently stabilized by peptide adsorption to the pore edges. This disruption to the membrane is presumably responsible for cell death. Amyloidal peptides also show evidence of stable large pore formation, however, the mechanism for pore stabilization appears linked with their ability to form fibrils and prefibrillar aggregates and oligomers. There is some evidence that pores and membrane defects in fact act as nucleation sites for these structures. Where possible we have related the experimental and theoretical work to our own simulation findings in an effort to produce a comprehensive, albeit speculative picture for the mechanisms of action for this important group of peptides.
Export Options
About this article
Cite this article as:
Sun Delin, Forsman Jan and Woodward E. Clifford, Current Understanding of the Mechanisms by which Membrane-Active Peptides Permeate and Disrupt Model Lipid Membranes, Current Topics in Medicinal Chemistry 2016; 16 (2) . https://dx.doi.org/10.2174/1568026615666150812121241
DOI https://dx.doi.org/10.2174/1568026615666150812121241 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Hepatoprotective Effects of Resveratrol in Non-Alcoholic Fatty Live Disease
Current Pharmaceutical Design GSK-3 Inhibitors: Discoveries and Developments
Current Medicinal Chemistry Pathogenetic Correction of the Enteric Insufficiency Syndrome in Patients with Advanced Peritonitis
Reviews on Recent Clinical Trials Human postnatal Mesenchymal Stem Cell Derived Islets as a Model for Diabetes Research
Current Diabetes Reviews The Involvement of PPARs in the Causes, Consequences and Mechanisms for Correction of Cardiac Lipotoxicity and Oxidative Stress
Current Molecular Pharmacology Autologous Circulating Progenitor Cells Transplanted with Hybrid Scaffold Accelerate Diabetic Wound Healing in Rabbit Model
Current Tissue Engineering (Discontinued) High-dose Vitamin D Supplementation on Type 1 Diabetes Mellitus Patients: Is there an Improvement in Glycemic Control?
Current Diabetes Reviews Model for Gestational Diabetes on Web Based Parameters
Recent Patents on Engineering Sorbitol Dehydrogenase: Structure, Function and Ligand Design
Current Medicinal Chemistry Physiologic Versus Diabetogenic Effects of Interleukin-1: A Question of Weight
Current Pharmaceutical Design Tigecycline: A New Treatment Choice Against Acinetobacter baumannii
Recent Patents on Anti-Infective Drug Discovery New Pharmacologic Approaches to Prevent Thromboembolism in Patients with Atrial Fibrillation
Current Vascular Pharmacology Statistical Optimization of Pharmacogenomics Association Studies: Key Considerations from Study Design to Analysis
Current Pharmacogenomics and Personalized Medicine Long-Term Extensions of Randomized Vaccination Trials of ACC-001 and QS-21 in Mild to Moderate Alzheimer’s Disease
Current Alzheimer Research A Practical Comprehensive Approach to Management of Acute Decompensated Heart Failure
Current Cardiology Reviews Development of Insulin Resistance During Aging: Involvement of Central Processes and Role of Adipokines
Current Protein & Peptide Science Assessment of Cardiac Performance with Magnetic Resonance Imaging
Current Cardiology Reviews Modulation of Hematological Indices of Normal and Alloxan-Induced Diabetic Rabbits by Aqueous Extract of Pleurotus tuberregium Sclerotia
Endocrine, Metabolic & Immune Disorders - Drug Targets Why and How We Should Treat Elderly Patients with Hypertension?
Current Vascular Pharmacology Plasma Acetylcholinesterase Activity Correlates with Intracerebral β-Amyloid Load
Current Alzheimer Research