Abstract
Lipopolysaccharide (LPS), the glycolipid of the outer membrane of Gram-negative bacteria, is critically involved in health and diseases. LPS facilitates the survival of pathogens by imposing a permeability barrier against antibiotics and antimicrobial peptides. LPS, also termed as endotoxin, functions as a potent inducer of innate immunity. Interception of endotoxin in systemic circulation by immune cells e.g. macrophages is essential to mount surveillance against invading microbes. However, a hyper-activated immune response may lead to the overwhelming production of tissue damaging cytokines TNF-α, IL-1, IL-6 and free radicals that may cause multiple organ failures or septic shock syndromes. The sepsis or septic shock is the major cause of mortality; 120,000 deaths/year occur in the United States alone, in the intensive care units. To-date, no therapeutic is available to combat sepsis mediated lethality. Furthermore, bacterial resistance against commonly used antibiotics has been increasing at an alarming rate necessitating a search for antibacterial agents with novel mode of actions. LPS could be a valid drug target for the development of antiendotoxic and antimicrobial compounds. In this article, recent advances in structural basis of LPS recognition by its receptor proteins and mode of actions of antimicrobial peptides defensins and cathelicidins are reviewed. Our research has identified, through de novo design, antimicrobial and endotoxin interacting β-boomerang peptides. Structure-activity correlations (SAR) of these peptides have been discussed, highlighting future design to achieve potent LPS neutralizing molecules.
Keywords: Lipopolysaccharide, antimicrobial peptide, de novo designed peptide, endotoxin, sepsis, NMR, tr-NOE, STD-NMR
Current Medicinal Chemistry
Title: De novo Designed Lipopolysaccharide Binding Peptides: Structure Based Development of Antiendotoxic and Antimicrobial Drugs
Volume: 17 Issue: 27
Author(s): S. Bhattacharjya
Affiliation:
Keywords: Lipopolysaccharide, antimicrobial peptide, de novo designed peptide, endotoxin, sepsis, NMR, tr-NOE, STD-NMR
Abstract: Lipopolysaccharide (LPS), the glycolipid of the outer membrane of Gram-negative bacteria, is critically involved in health and diseases. LPS facilitates the survival of pathogens by imposing a permeability barrier against antibiotics and antimicrobial peptides. LPS, also termed as endotoxin, functions as a potent inducer of innate immunity. Interception of endotoxin in systemic circulation by immune cells e.g. macrophages is essential to mount surveillance against invading microbes. However, a hyper-activated immune response may lead to the overwhelming production of tissue damaging cytokines TNF-α, IL-1, IL-6 and free radicals that may cause multiple organ failures or septic shock syndromes. The sepsis or septic shock is the major cause of mortality; 120,000 deaths/year occur in the United States alone, in the intensive care units. To-date, no therapeutic is available to combat sepsis mediated lethality. Furthermore, bacterial resistance against commonly used antibiotics has been increasing at an alarming rate necessitating a search for antibacterial agents with novel mode of actions. LPS could be a valid drug target for the development of antiendotoxic and antimicrobial compounds. In this article, recent advances in structural basis of LPS recognition by its receptor proteins and mode of actions of antimicrobial peptides defensins and cathelicidins are reviewed. Our research has identified, through de novo design, antimicrobial and endotoxin interacting β-boomerang peptides. Structure-activity correlations (SAR) of these peptides have been discussed, highlighting future design to achieve potent LPS neutralizing molecules.
Export Options
About this article
Cite this article as:
Bhattacharjya S., De novo Designed Lipopolysaccharide Binding Peptides: Structure Based Development of Antiendotoxic and Antimicrobial Drugs, Current Medicinal Chemistry 2010; 17 (27) . https://dx.doi.org/10.2174/092986710791959756
DOI https://dx.doi.org/10.2174/092986710791959756 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
The Kidney and the Sympathetic System: A Short Review
Current Clinical Pharmacology Method Validation and Simultaneous Determination of Retinol, Retinyl Palmitate, β-Carotene, α-Tocopherol and Vitamin C in Rat Serum Treated with 7,12 Dimethylbenz[a]Anthracene and Plantago major L. by High- Performance Liquid Chromatography Using Diode-Array Detection
Combinatorial Chemistry & High Throughput Screening To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and Nitrite in Health and Illness
Reviews on Recent Clinical Trials Update on the Adverse Effects of Clozapine: Focus on Myocarditis
Current Drug Safety Purinergic Signalling and Endothelium
Current Vascular Pharmacology Compendious Review on Bioactive Constituents and Pharmacotherapeutic Profile of Heliotropium indicum Linn
The Natural Products Journal Levosimendan for Heart-Operated Patients: What is the State of the Art?
Recent Patents on Cardiovascular Drug Discovery Nicotine and Nicotinic Receptor Involvement in Neuropsychiatric Disorders
Current Topics in Medicinal Chemistry Effects of <i>Nigella Sativa</i> (Black seeds) Supplementation on Plasma Lipid Profile in Human Subjects - A Review
Current Nutraceuticals Annona sp: Plants with Multiple Applications as Alternative Medicine - A Review
Current Bioactive Compounds Anti-Tumor Necrosis Factor-Alpha (TNF-α) Treatment Strategies in Crohns Disease
Recent Patents on Inflammation & Allergy Drug Discovery Mechanisms of Interferon Mediated Anti-Viral Resistance
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Pharmacogenetically Tailored Treatments for Heart Disease
Current Pharmaceutical Design A Safe and Novel Desensitization Protocol with Ferric Carboxymaltose to Treat Iron Deficiency Anemia
Current Drug Safety Potential Benefits and Limits of Psychopharmacological Therapies in Pervasive Developmental Disorders
Current Clinical Pharmacology Epigenetic Drugs in Cognitive Disorders
Current Pharmaceutical Design Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection
Current Pharmaceutical Design Polypharmacology of <i>Aconitum</i> and <i>Delphinium</i> sp. Diterpene Alka loids: Antiarrhythmic, Analgesic and Anti-Inflammatory Effects
Mini-Reviews in Organic Chemistry Clinical and Forensic Aspects of Pharmacobezoars
Current Drug Research Reviews Dark Chocolate and Blood Pressure: A Novel Study from Jordan
Current Drug Delivery