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
-
Recent Developments on Phenstatins as Potent Antimitotic Agents
Current Medicinal Chemistry Agonists and Antagonists Acting at P2X7 Receptor
Current Topics in Medicinal Chemistry Proactive Aquatic Ecotoxicological Assessment of Room-Temperature Ionic Liquids
Current Organic Chemistry Ferroptosis Inducers for Prostate Cancer Therapy
Current Medicinal Chemistry Measuring the Infectiousness of Persons with HIV-1: Opportunities for Preventing Sexual HIV-1 Transmission
Current HIV Research A Review on Biological Properties and Synthetic Methodologies of Diarylpentadienones
Mini-Reviews in Medicinal Chemistry Endocannabinoid Binding to the Cannabinoid Receptors: What Is Known and What Remains Unknown
Current Medicinal Chemistry Unsupervised End-to-End Brain Tumor Magnetic Resonance Image Registration Using RBCNN: Rigid Transformation, B-Spline Transformation and Convolutional Neural Network
Current Medical Imaging COVID-19 Associated Pancytopenia (CAP): A Clinical Impact
Recent Advances in Inflammation & Allergy Drug Discovery Synergy of microRNA and Stem Cell: A Novel Therapeutic Approach for Diabetes Mellitus and Cardiovascular Diseases
Current Diabetes Reviews Targeting Virus-host Interactions of HIV Replication
Current Topics in Medicinal Chemistry Molecular Docking and Quantum Studies of Lawsone Dimers Derivatives: New Investigation of Antioxidant Behavior and Antifungal Activity
Current Topics in Medicinal Chemistry Immunomodulatory Effects of <i>Allium sativum</i> L. and its Constituents against Viral Infections and Metabolic Diseases
Current Topics in Medicinal Chemistry A QSAR Study of Biphenyl Analogues of 2-Nitroimidazo-[2, 1-b] [1, 3] - oxazines as Antitubercular Agents Using Genetic Function Approximation
Medicinal Chemistry Neuroprotective Role of Nanoparticles Against Alzheimer's Disease
Current Drug Metabolism Building Biological Complexity with Limited Genes
Current Genomics Fluoroquinolones as Chemotherapeutics Against Mycobacterial Infections
Current Pharmaceutical Design Modulation of GABAA Receptors by Natural Products and the Development of Novel Synthetic Ligands for the Benzodiazepine Binding Site
Current Drug Targets Self-Medication and Storage of Drugs at Home Among the Clients of Drugstores in Tabriz
Current Drug Safety Bioactivity of New μ and δ Opioid Peptides
Medicinal Chemistry