Abstract
Lipopolysaccharide (LPS) induced Gram-negative sepsis and septic shock remain lethal in up to 60 % of cases, and LPS antagonists that neutralize its endotoxic action are the subject of intensive research. The molecular motifs of specific binding of LPS by antiendotoxin proteins and peptides may lead to an understanding of LPS action at the atomic level and provide clues for the development of new immunomodulatory compounds for use as therapy in the treatment of Gram-negative bacterial sepsis. The interaction of LPS with its cognate binding proteins has been structurally elucidated in the single case of the X-ray crystallographic structure of LPS in complex with the integral outer membrane protein FhuA from E. coli K-12 (Ferguson et al., Science 1999, 282, 2215). This structure and other known structures of LPS binding proteins have been used to propose a common binding motif of LPS to proteins. Another independent source of structural information are solution structures of peptides in complex with LPS that can be determined using the transferred NOE effect. The molecular mechanisms of biological activity of bacterial endotoxins can additionally be probed by theoretical means. The growing structural knowledge is opening pathways to the design of peptides or peptidomimetics with improved antiendotoxin properties.
Keywords: lipopolysaccharide (lps), septic shock, lps inhibiting proteins, lps inhibiting peptides, molecular recognition
Current Topics in Medicinal Chemistry
Title: The Search for Molecular Determinants of LPS Inhibition by Proteins and Peptides
Volume: 4 Issue: 11
Author(s): Primoz Pristovsek and Jurka Kidric
Affiliation:
Keywords: lipopolysaccharide (lps), septic shock, lps inhibiting proteins, lps inhibiting peptides, molecular recognition
Abstract: Lipopolysaccharide (LPS) induced Gram-negative sepsis and septic shock remain lethal in up to 60 % of cases, and LPS antagonists that neutralize its endotoxic action are the subject of intensive research. The molecular motifs of specific binding of LPS by antiendotoxin proteins and peptides may lead to an understanding of LPS action at the atomic level and provide clues for the development of new immunomodulatory compounds for use as therapy in the treatment of Gram-negative bacterial sepsis. The interaction of LPS with its cognate binding proteins has been structurally elucidated in the single case of the X-ray crystallographic structure of LPS in complex with the integral outer membrane protein FhuA from E. coli K-12 (Ferguson et al., Science 1999, 282, 2215). This structure and other known structures of LPS binding proteins have been used to propose a common binding motif of LPS to proteins. Another independent source of structural information are solution structures of peptides in complex with LPS that can be determined using the transferred NOE effect. The molecular mechanisms of biological activity of bacterial endotoxins can additionally be probed by theoretical means. The growing structural knowledge is opening pathways to the design of peptides or peptidomimetics with improved antiendotoxin properties.
Export Options
About this article
Cite this article as:
Pristovsek Primoz and Kidric Jurka, The Search for Molecular Determinants of LPS Inhibition by Proteins and Peptides, Current Topics in Medicinal Chemistry 2004; 4 (11) . https://dx.doi.org/10.2174/1568026043388105
DOI https://dx.doi.org/10.2174/1568026043388105 |
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
-
Simultaneous Amplification of HER-2 (ERBB2) and Topoisomerase IIα (TOP2A) Genes - Molecular Basis for Combination Chemotherapy in Cancer
Current Cancer Drug Targets Antioxidant Properties and Associated Mechanisms of Salicylates
Current Medicinal Chemistry Kavalactone Pharmacophores for Major Cellular Drug Targets
Mini-Reviews in Medicinal Chemistry cGAS-STING-mediated IFN-I Response in Host Defense and Neuroinflammatory Diseases
Current Neuropharmacology DNA Vaccine and the CNS Axonal Regeneration
Current Pharmaceutical Design Dietary Polyphenols for Prostate Cancer Therapy
Current Bioactive Compounds Immune-Mediated Mechanisms in Atherosclerosis: Prevention and Treatment of Clinical Manifestations
Current Pharmaceutical Design Triamcinolone Acetonide Inhibits p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy
Current Molecular Medicine Targeting Angiogenesis in Gastro-Intestinal Non Colorectal Cancers; A Review
Current Angiogenesis (Discontinued) Cyclooxygenase-2 Biology
Current Pharmaceutical Design The Role of Arthroscopy in Wrist Arthritis
Current Rheumatology Reviews How Current Direct-Acting Antiviral and Novel Cell Culture Systems for HCV are Shaping Therapy and Molecular Diagnosis of Chronic HCV Infection?
Current Drug Targets Cancer Immunotherapy: The Role Regulatory T Cells Play and What Can be Done to Overcome their Inhibitory Effects
Current Molecular Medicine AT2 Receptor Agonists: Exploiting the Beneficial Arm of Ang II Signaling
Current Hypertension Reviews Subject Index to Volume 10
Current Pharmaceutical Design Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology The Role of Non-coding Genome in Cancer-associated Fibroblasts; Stateof- the-Art and Perspectives in Cancer Targeted Therapy
Current Drug Targets New Generation Calcium Channel Blockers in Hypertensive Treatment
Current Hypertension Reviews A Practical Comprehensive Approach to Management of Acute Decompensated Heart Failure
Current Cardiology Reviews Induced Adaptive Resistance to Nitrooxidative Stress in the CNS: Therapeutic Implications
Central Nervous System Agents in Medicinal Chemistry