Abstract
Antimicrobial peptides (AMPs) are showing increasing promise as potential candidate antibacterial drugs in the face of the rapidly emerging bacterial resistance to conventional antibiotics in recent years. The target of these peptides is the microbial membrane and there are numerous models to explain their mechanism of action ranging from pore formation to general membrane disruption. The interaction between the AMP and the target membrane is critical to the specificity and activity of these peptides. However, a precise understanding of the relationship between antimicrobial peptide structure and their cytolytic function in a range of organisms is still lacking. This is a result of the complex nature of the interactions of AMPs with the cell membrane, the mechanism of which can vary considerably between different classes of antimicrobia peptides. A wide range of biophysical techniques have been used to study the influence of a number of peptide and membrane properties on the cytolytic activity of these peptides in model membrane systems. Central to characterisation of this interaction is a quantitative analysis of the binding of peptide to the membrane and the coherent dynamic changes in membrane structure. Recently, dual polarization interferometry has been used to perform an in depth analysis of antimicrobial peptide induced membrane perturbation and with new mass-structure co-fitting kinetic analysis have allowed a real-time label free analysis of binding affinity and kinetics. We review these studies which describe multi-step mechanisms which are adopted by various AMPs in nature and may advance our approach to the development of a new generation of effective antimicrobial therapeutics.
Keywords: Antimicrobial peptides, dual polarisation interferometry, membrane bilayer anisotropy, membrane structure plasticity, supported lipid bilayer.
Current Topics in Medicinal Chemistry
Title:Antimicrobial Peptide Structure and Mechanism of Action: A Focus on the Role of Membrane Structure
Volume: 16 Issue: 1
Author(s): Tzong-Hsien Lee, Kristopher N. Hall and Marie-Isabel Aguilar
Affiliation:
Keywords: Antimicrobial peptides, dual polarisation interferometry, membrane bilayer anisotropy, membrane structure plasticity, supported lipid bilayer.
Abstract: Antimicrobial peptides (AMPs) are showing increasing promise as potential candidate antibacterial drugs in the face of the rapidly emerging bacterial resistance to conventional antibiotics in recent years. The target of these peptides is the microbial membrane and there are numerous models to explain their mechanism of action ranging from pore formation to general membrane disruption. The interaction between the AMP and the target membrane is critical to the specificity and activity of these peptides. However, a precise understanding of the relationship between antimicrobial peptide structure and their cytolytic function in a range of organisms is still lacking. This is a result of the complex nature of the interactions of AMPs with the cell membrane, the mechanism of which can vary considerably between different classes of antimicrobia peptides. A wide range of biophysical techniques have been used to study the influence of a number of peptide and membrane properties on the cytolytic activity of these peptides in model membrane systems. Central to characterisation of this interaction is a quantitative analysis of the binding of peptide to the membrane and the coherent dynamic changes in membrane structure. Recently, dual polarization interferometry has been used to perform an in depth analysis of antimicrobial peptide induced membrane perturbation and with new mass-structure co-fitting kinetic analysis have allowed a real-time label free analysis of binding affinity and kinetics. We review these studies which describe multi-step mechanisms which are adopted by various AMPs in nature and may advance our approach to the development of a new generation of effective antimicrobial therapeutics.
Export Options
About this article
Cite this article as:
Lee Tzong-Hsien, Hall N. Kristopher and Aguilar Marie-Isabel, Antimicrobial Peptide Structure and Mechanism of Action: A Focus on the Role of Membrane Structure, Current Topics in Medicinal Chemistry 2016; 16 (1) . https://dx.doi.org/10.2174/1568026615666150703121700
DOI https://dx.doi.org/10.2174/1568026615666150703121700 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Chemical and Medicinal Versatility of Substituted 1,4-Dihydropyridines
Current Bioactive Compounds New Insights into Ocular Complications of Human Immunodeficiency Virus Infection
Current HIV Research Identification of Active Phytochemical from Traditional Herbal Knowledge-base Targeting Pantothenate Synthetase for Anti-tuberculosis Therapy
Letters in Drug Design & Discovery Editorial (Thematic Issue: Recent Updates on Biologically Active Heterocycles - Part 2)
Current Organic Chemistry Application, Reactivity and Synthesis of Isoxazole Derivatives
Mini-Reviews in Organic Chemistry Long-Term CD4 Cell Count Recovery among Thai Naive HIV-Infected Patients Initiating HAART at Low CD4 Cell Count
Current HIV Research Biological Properties of Yeast-based Mannoprotein for Prospective Biomedical Applications
Combinatorial Chemistry & High Throughput Screening Clear Shot at Primary Aim: Susceptibility of Trypanosoma cruzi Organelles, Structures and Molecular Targets to Drug Treatment
Current Topics in Medicinal Chemistry MRI of the Small and Large Bowel
Current Medical Imaging The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders
Inflammation & Allergy - Drug Targets (Discontinued) New Patentable Use of an Old Neuroleptic Compound Thioridazine to Combat Tuberculosis: A Gene Regulation Perspective
Recent Patents on Anti-Infective Drug Discovery Differential Gene Expression of <i>ASUN, NEMF, PTPRC</i> and <i>DHX29</i>: Candidate Biomarkers for the Diagnosis of Active and Latent Tuberculosis
Infectious Disorders - Drug Targets Natural Resins and Bioactive Natural Products thereof as Potential Anitimicrobial Agents
Current Pharmaceutical Design Identification and Validation of Novel Drug Targets in Tuberculosis
Current Pharmaceutical Design Adaptors in Toll-Like Receptor Signaling and their Potential as Therapeutic Targets
Current Drug Targets The Effect of Pyrroloquinoline Quinone on Apoptosis and Autophagy in Traumatic Brain Injury
CNS & Neurological Disorders - Drug Targets Treatment Options in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders
Current Pharmaceutical Design Evaluation of Serine Protease Inhibitors as Potent FVIIa-sTF Inhibitors in the Blood Coagulation Cascade
Letters in Drug Design & Discovery Drug Evolution Concept in Drug Design: 2. Chimera Method
Medicinal Chemistry Significance of Lipolytic Enzymes in Pathogenesis and Treatment of Neglected Diseases
Current Protein & Peptide Science