Abstract
Small molecule inhibition of HIV fusion has been an elusive goal, despite years of effort by both pharmaceutical and academic laboratories. In this review, we will discuss the amphipathic properties of both peptide and small molecule inhibitors of gp41-mediated fusion. Many of the peptides and small molecules that have been developed target a large hydrophobic pocket situated within the grooves of the coiled coil, a potential hotspot for inhibiting the trimer of hairpin formation that accompanies fusion. Peptide studies reveal molecular properties required for effective inhibition, including elongated structure and lipophilic or amphiphilic nature. The characteristics of peptides that bind in this pocket provide features that should be considered in small molecule development. Additionally, a novel site for small molecule inhibition of fusion has recently been suggested, involving residues of the loop and fusion peptide. We will review the small molecule structures that have been developed, evidence pointing to their mechanism of action and strategies towards improving their affinity. The data points to the need for a strongly amphiphilic character of the inhibitors, possibly as a means to mediate the membrane - protein interaction that occurs in gp41 in addition to the protein – protein interaction that accompanies the fusion-activating conformational transition.
Keywords: HIV-1, gp41, inhibition, small molecules, amphiphilic, hydrophobic pocket, Small molecule inhibition, amphipathic properties, gp41-mediated fusion, affinity, membrane - protein interaction, fusion-activating conformational transition
Current Topics in Medicinal Chemistry
Title: Amphipathic Properties of HIV-1 gp41 Fusion Inhibitors
Volume: 11 Issue: 24
Author(s): Miriam Gochin and Guangyan Zhou
Affiliation:
Keywords: HIV-1, gp41, inhibition, small molecules, amphiphilic, hydrophobic pocket, Small molecule inhibition, amphipathic properties, gp41-mediated fusion, affinity, membrane - protein interaction, fusion-activating conformational transition
Abstract: Small molecule inhibition of HIV fusion has been an elusive goal, despite years of effort by both pharmaceutical and academic laboratories. In this review, we will discuss the amphipathic properties of both peptide and small molecule inhibitors of gp41-mediated fusion. Many of the peptides and small molecules that have been developed target a large hydrophobic pocket situated within the grooves of the coiled coil, a potential hotspot for inhibiting the trimer of hairpin formation that accompanies fusion. Peptide studies reveal molecular properties required for effective inhibition, including elongated structure and lipophilic or amphiphilic nature. The characteristics of peptides that bind in this pocket provide features that should be considered in small molecule development. Additionally, a novel site for small molecule inhibition of fusion has recently been suggested, involving residues of the loop and fusion peptide. We will review the small molecule structures that have been developed, evidence pointing to their mechanism of action and strategies towards improving their affinity. The data points to the need for a strongly amphiphilic character of the inhibitors, possibly as a means to mediate the membrane - protein interaction that occurs in gp41 in addition to the protein – protein interaction that accompanies the fusion-activating conformational transition.
Export Options
About this article
Cite this article as:
Gochin Miriam and Zhou Guangyan, Amphipathic Properties of HIV-1 gp41 Fusion Inhibitors, Current Topics in Medicinal Chemistry 2011; 11 (24) . https://dx.doi.org/10.2174/156802611798808488
DOI https://dx.doi.org/10.2174/156802611798808488 |
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
-
Synthetic Src-Kinase Domain Inhibitors and Their Structural Requirements
Anti-Cancer Agents in Medicinal Chemistry Repurposing Ruxolitinib in Combating COVID-19: A Mini-review
New Emirates Medical Journal Prevention of Contrast Induced Nephropathy
Current Drug Therapy NMR Screening and Hit Validation in Fragment Based Drug Discovery
Current Topics in Medicinal Chemistry Designing Drugs on the Internet? Free Web Tools and Services Supporting Medicinal Chemistry
Current Topics in Medicinal Chemistry Stemming Epigenetics in Marine Stramenopiles
Current Genomics A Brief Review of Radiofrequency Coils for Cardiac Magnetic Resonance Imaging and Spectroscopy
Current Medical Imaging Drug-Induced Pulmonary Hypertension in Newborns: A Review.
Current Vascular Pharmacology Development of Improved Factor VIII Molecules and New Gene Transfer Approaches for Hemophilia A
Current Gene Therapy <i>In-silico</i> Analysis of Angiotensin-converting Enzyme 2 (ACE2) of Livestock, Pet and Poultry Animals to Determine its Susceptibility to SARS–CoV- 2 Infection
Combinatorial Chemistry & High Throughput Screening Antagonists of IAP Proteins: Novel Anti-Tumor Agents
Current Medicinal Chemistry Beyond the Direct Activation of Cannabinoid Receptors: New Strategies to Modulate the Endocannabinoid System in CNS-Related Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Good Uptake of the COVID-19 Vaccine among Patients with Rheumatic Diseases in the United Arab Emirates (UAE)
New Emirates Medical Journal Immunity Modulators, Repurposed Drugs and Candidate Vaccines for COVID-19: A Review
Coronaviruses COVID-19: A Great Mime or a Trigger Event of Autoimmune Manifestations?
Current Rheumatology Reviews Transcriptional Regulation of Antimicrobial Host Defense Peptides
Current Protein & Peptide Science CRISPeering: Bioengineering the Host Cells through CRISPRCas9 Genome Editing System as the Next-generation of Cell Factories
Recent Patents on Biotechnology Is Amyloid Binding Alcohol Dehydrogenase a Drug Target for Treating Alzheimer’s Disease?
Current Alzheimer Research Impact of COVID-19 on Mental Dimension of Health: A Sensitive Issue to be Addressed at the Earliest
Current Psychiatry Research and Reviews The Prediction of Carcinogenicity from Molecular Structure
Current Computer-Aided Drug Design