Abstract
Correcting aberrant folds that develop during protein folding disease states is now an active research endeavor that is attracting increasing attention from both academic and industrial circles. One particular approach focuses on developing or identifying small molecule correctors or pharmacological chaperones that specifically stabilize the native fold. Unfortunately, the limited screening platforms available to rapidly identify or validate potential drug candidates are usually inadequate or slow because the folding disease proteins in question are often transiently folded and/or aggregationprone, complicating and/or interfering with the assay outcomes. In this review, we outline and discuss the numerous platform options currently being employed to identify small molecule therapeutics for folding diseases. Finally, we describe a new stability screening approach that is broad based and is easily applicable toward a very large number of both common and rare protein folding diseases. The label free screening method described herein couples the promiscuity of the GroEL binding to transient aggregation-prone hydrophobic folds with surface plasmon resonance enabling one to rapidly identify potential small molecule pharmacological chaperones.
Keywords: Protein misfolding, missense mutations, pharmacological chaperones, GroEL chaperonin, Surface Plasmon Resonance
Current Topics in Medicinal Chemistry
Title:On the Design of Broad Based Screening Assays to Identify Potential Pharmacological Chaperones of Protein Misfolding Diseases
Volume: 12 Issue: 22
Author(s): Subhashchandra Naik, Na Zhang, Phillip Gao and Mark T. Fisher
Affiliation:
Keywords: Protein misfolding, missense mutations, pharmacological chaperones, GroEL chaperonin, Surface Plasmon Resonance
Abstract: Correcting aberrant folds that develop during protein folding disease states is now an active research endeavor that is attracting increasing attention from both academic and industrial circles. One particular approach focuses on developing or identifying small molecule correctors or pharmacological chaperones that specifically stabilize the native fold. Unfortunately, the limited screening platforms available to rapidly identify or validate potential drug candidates are usually inadequate or slow because the folding disease proteins in question are often transiently folded and/or aggregationprone, complicating and/or interfering with the assay outcomes. In this review, we outline and discuss the numerous platform options currently being employed to identify small molecule therapeutics for folding diseases. Finally, we describe a new stability screening approach that is broad based and is easily applicable toward a very large number of both common and rare protein folding diseases. The label free screening method described herein couples the promiscuity of the GroEL binding to transient aggregation-prone hydrophobic folds with surface plasmon resonance enabling one to rapidly identify potential small molecule pharmacological chaperones.
Export Options
About this article
Cite this article as:
Naik Subhashchandra, Zhang Na, Gao Phillip and T. Fisher Mark, On the Design of Broad Based Screening Assays to Identify Potential Pharmacological Chaperones of Protein Misfolding Diseases, Current Topics in Medicinal Chemistry 2012; 12 (22) . https://dx.doi.org/10.2174/1568026611212220006
DOI https://dx.doi.org/10.2174/1568026611212220006 |
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
-
Natural Antioxidants: Therapeutic Prospects for Cancer and Neurological Diseases
Mini-Reviews in Medicinal Chemistry Minocycline: Neuroprotective Mechanisms in Parkinsons Disease
Current Pharmaceutical Design Clinical Uses of Melatonin: Evaluation of Human Trials
Current Medicinal Chemistry Multifunctional Nanoparticles, Nanocages and Degradable Polymers as a Potential Novel Generation of Non-Invasive Molecular and Cellular Imaging Systems
Recent Patents on Nanotechnology Pathologically-Activated Therapeutics for Neuroprotection: Mechanism of NMDA Receptor Block by Memantine and S-Nitrosylation
Current Drug Targets Structural Activity Relationship and Importance of Benzothiazole Derivatives in Medicinal Chemistry: A Comprehensive Review
Mini-Reviews in Organic Chemistry Stem Cell Pharmacogenomics
Current Topics in Medicinal Chemistry Pharmacoperones as a New Therapeutic Approach: In Vitro Identification and In vivo Validation of Bioactive Molecules
Current Drug Targets Neuro-Transmitters in the Central Nervous System & their Implication in Learning and Memory Processes
Current Medicinal Chemistry P2Y Receptors in the Mammalian Nervous System: Pharmacology, Ligands and Therapeutic Potential
CNS & Neurological Disorders - Drug Targets Spin Trapping: An Essential Tool for the Study of Diseases Caused by Oxidative Stress
Current Topics in Medicinal Chemistry From Stem Cells to Dopamine Neurons: Developmental Biology Meets Neurodegeneration
CNS & Neurological Disorders - Drug Targets Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences
Current Cardiology Reviews Molecular Pharmacology of the Glycine Receptor Chloride Channel
Current Pharmaceutical Design p75NTR as a Therapeutic Target for Neuropsychiatric Diseases
Current Molecular Pharmacology Molecular Insight into the Crosstalk of UPS Components and Alzheimer’s Disease
Current Protein & Peptide Science The Role of Autophagy on the Survival of Dopamine Neurons
Current Topics in Medicinal Chemistry ABC Transporters in Neurological Disorders: An Important Gateway for Botanical Compounds Mediated Neuro-Therapeutics
Current Topics in Medicinal Chemistry Pharmacological Applications of Antioxidants: Lights and Shadows
Current Drug Targets HSP27: Mechanisms of Cellular Protection Against Neuronal Injury
Current Molecular Medicine