Abstract
Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant RT forms. Previous crystal complex structures of HIV-1 RT revealed the interaction mechanism between the enzyme and inhibitors, which promoted the exploitation of inhibitor that had sufficient conformational flexibility to combat resistance. Hence, the potential flexibility of a drug should be part of the strategy considered in the early stages of designing drugs that are intended to be broadly effective against mutated targets associated with drug resistance. This review provides an overview of the state of the art in this field, including design strategies and challenges for medicinal chemists.
Keywords: HIV Reverse transcriptase, conformational flexibility, drug resistance.
Current Pharmaceutical Design
Title:Structure-based Design of Conformationally Flexible Reverse Transcriptase Inhibitors to Combat Resistant HIV
Volume: 20 Issue: 5
Author(s): Ge-Fei Hao, Sheng-Gang Yang and Guang-Fu Yang
Affiliation:
Keywords: HIV Reverse transcriptase, conformational flexibility, drug resistance.
Abstract: Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 RT agents that have improved potency and efficacy against the wild-type (WT) RT, but also target resistant RT forms. Previous crystal complex structures of HIV-1 RT revealed the interaction mechanism between the enzyme and inhibitors, which promoted the exploitation of inhibitor that had sufficient conformational flexibility to combat resistance. Hence, the potential flexibility of a drug should be part of the strategy considered in the early stages of designing drugs that are intended to be broadly effective against mutated targets associated with drug resistance. This review provides an overview of the state of the art in this field, including design strategies and challenges for medicinal chemists.
Export Options
About this article
Cite this article as:
Hao Ge-Fei, Yang Sheng-Gang and Yang Guang-Fu, Structure-based Design of Conformationally Flexible Reverse Transcriptase Inhibitors to Combat Resistant HIV, Current Pharmaceutical Design 2014; 20 (5) . https://dx.doi.org/10.2174/138161282005140214163439
DOI https://dx.doi.org/10.2174/138161282005140214163439 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
-
Controlled Release of Insulin in Blood from Strontium-Substituted Carbonate Apatite Complexes
Current Drug Delivery Regulators of the G1 Phase of the Cell Cycle and Neurogenesis
Central Nervous System Agents in Medicinal Chemistry Anticancer Antioxidant Regulatory Functions of Phytochemicals
Current Medicinal Chemistry Systemic and Biophase Bioavailability and Pharmacokinetics of Nanoparticulate Drug Delivery Systems
Current Drug Delivery Analysis of Current Antifungal Agents and Their Targets within the Pneumocystis carinii Genome
Current Drug Targets Bacterial Protein Microarrays for Diagnosis of Infectious Diseases
Current Immunology Reviews (Discontinued) Design, Synthesis and Biological Evaluation of Pyrido[2,3-d] Pyrimidine Derivatives as Potential Anticancer Agents
Letters in Drug Design & Discovery The Impact of Computer Science in Molecular Medicine: Enabling High- Throughput Research
Current Topics in Medicinal Chemistry Applicability and Approaches of (Meth) Acrylate Copolymers (Eudragits) in Novel Drug Delivery Systems
Current Drug Therapy Estrogen Receptor Polymorphisms: Significance to Human Physiology, Disease and Therapy
Recent Patents on DNA & Gene Sequences Infection and Malignancy Risk in Patients Treated with TNF Inhibitors for Immune-Mediated Inflammatory Diseases
Current Drug Safety Targeting Vascular Redox Biology Through Antioxidant Gene Delivery: A Historical View and Current Perspectives
Recent Patents on Cardiovascular Drug Discovery Recent Patents in X-Ray Phase Contrast Imaging
Recent Patents on Biomedical Engineering (Discontinued) Cardiotoxicity of Molecularly Targeted Agents
Current Cardiology Reviews Recent Patents Review in Microencapsulation of Pharmaceuticals Using the Emulsion Solvent Removal Methods
Recent Patents on Drug Delivery & Formulation Redox Control of Cardiovascular Homeostasis by Angiotensin II
Current Pharmaceutical Design Epigenetic Mechanisms in Alzheimer's Disease
Current Medicinal Chemistry Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation Prospects and Limitations of T Cell Receptor Gene Therapy
Current Gene Therapy The Inhibition of Cell Proliferation Using Silencing of N-Cadherin Gene by siRNA Process in Human Melanoma Cell Lines
Current Medicinal Chemistry