Abstract
The availability of new, highly selective antagonists, in the field of opioid peptides and of other pain peptides, is important both for a better understanding of the interaction of the receptors with their ligands and for their practical relevance. The design of antagonists is not obvious even when the essential features of agonists are well known. In this review we have examined the main aspects of the problem using, as leading criteria two theoretical models of antagonism and the subdivision of opioid peptides into two functional domains. The main causes of antagonism have been integrated in two very general models: one, referred to as the participation model, attributes antagonism to the lack, with respect to the parent agonist, of an essential group, whereas another model, attributes antagonism to the misfit of the molecule inside the receptor. The second criterion is the division of the structure of peptide hormones, originally put forward by Robert Schwyzer, in two functional domains, the message domain, which is responsible of the larger part of the binding affinity of opioid agonists, and an address domain, which dictates most of the peptide specificity. The most significant achievements in the design of opioid antagonists are classified according to the relative importance of chemical constitution, conformation and chirality.
Keywords: Opioid Peptides, antagonism
Current Topics in Medicinal Chemistry
Title: Antagonism in Opioid Peptides: the Role of Conformation
Volume: 4 Issue: 1
Author(s): Severo Salvadori and Piero A. Temussi
Affiliation:
Keywords: Opioid Peptides, antagonism
Abstract: The availability of new, highly selective antagonists, in the field of opioid peptides and of other pain peptides, is important both for a better understanding of the interaction of the receptors with their ligands and for their practical relevance. The design of antagonists is not obvious even when the essential features of agonists are well known. In this review we have examined the main aspects of the problem using, as leading criteria two theoretical models of antagonism and the subdivision of opioid peptides into two functional domains. The main causes of antagonism have been integrated in two very general models: one, referred to as the participation model, attributes antagonism to the lack, with respect to the parent agonist, of an essential group, whereas another model, attributes antagonism to the misfit of the molecule inside the receptor. The second criterion is the division of the structure of peptide hormones, originally put forward by Robert Schwyzer, in two functional domains, the message domain, which is responsible of the larger part of the binding affinity of opioid agonists, and an address domain, which dictates most of the peptide specificity. The most significant achievements in the design of opioid antagonists are classified according to the relative importance of chemical constitution, conformation and chirality.
Export Options
About this article
Cite this article as:
Salvadori Severo and A. Temussi Piero, Antagonism in Opioid Peptides: the Role of Conformation, Current Topics in Medicinal Chemistry 2004; 4 (1) . https://dx.doi.org/10.2174/1568026043451564
DOI https://dx.doi.org/10.2174/1568026043451564 |
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
-
Selenium Status in Elderly People: Longevity and Age-Related Diseases
Current Pharmaceutical Design Drugs and Rhabdomyolysis: From Liver to Kidney
Current Vascular Pharmacology From Surface to Nuclear Receptors: The Endocannabinoid Family Extends its Assets
Current Medicinal Chemistry Progress on Kinesin Spindle Protein Inhibitors as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Prevention of Endothelial Cell Injury by Activated Protein C: The Molecular Mechanism(s) and Therapeutic Implications
Current Vascular Pharmacology Predicting ADMET Properties by Projecting onto Chemical Space?Benefits and Pitfalls
Current Computer-Aided Drug Design Outcome and Complications of Hemoperfusion in Patients with COVID-19 in Intensive Care Unit: A Cross-Sectional Study
Cardiovascular & Hematological Agents in Medicinal Chemistry Possible Therapeutic Interventions in COVID-19 Induced ARDS by Cotinine as an ACE-2 Promoter and AT-1R Blocker
Infectious Disorders - Drug Targets Bacterial Sepsis and Chemokines
Current Drug Targets Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells
Anti-Cancer Agents in Medicinal Chemistry Antibacterial Activity and Structure-Activity Relationship Studies of 4- aryl/alkyl-1-(diphenylacetyl)thiosemicarbazides
Letters in Drug Design & Discovery Activated Surfaces for Laser Desorption Mass Spectrometry: Application for Peptide and Protein Analysis
Current Pharmaceutical Design Amiodarone - A ‘Broad Spectrum’ Antiarrhythmic Drug
Cardiovascular & Hematological Disorders-Drug Targets Autocorrelation of Molecular Electrostatic Potential Surface Properties Combined with Partial Least Squares Analysis as Alternative Attractive Tool to Generate Ligand-Based 3D-QSARs
Current Drug Discovery Technologies RNA Interference for Viral Infections
Current Drug Targets Recent Development in [1,4]Benzodiazepines as Potent Anticancer Agents: A Review
Mini-Reviews in Medicinal Chemistry Use of Psychotropics in COVID-19: Another Anti-inflammatory Pathway
Current Psychiatry Research and Reviews COVID-19: An Update on Pathogenesis and Treatment
Current Pharmaceutical Design Synthesis, Structure-Activity Relationship and Biological Activity of Acridine Derivatives as Potent MDR-Reversing Agents
Current Medicinal Chemistry Hit Triage Using Efficiency Indices after Screening of Compound Libraries in Drug Discovery
Current Topics in Medicinal Chemistry