Abstract
The renaissance of cell- or organism-based phenotypic assays has made subsequent target identification for bioactive small organic molecules an important aspect of current drug discovery. Among the many strategies available for target identification, derivatizing bioactive small molecules into activity-based probes has the main advantage of determining small molecule-protein interactions directly in the native environment where the target proteins maintain their three-dimensional structures, including all the post-translational modifications, as the discrete small molecular probes usually have better access to intracellular compartments. Thus this chemical platform will not only afford a more precise means of understanding the mechanisms of action for bioactive molecules, but shed light onto the specificity of the bioactive small molecules. Here we will provide an overview of the strategies for the design of activity-based small molecular probes and review their applications for target identification using case studies. Special emphasis is placed on logistic concerns for probes design as well as recent developments in this field.
Keywords: Target identification, phenotypic assay, activity-based probe, structure-activity relationship, radioisotope, biotin, fluorophore, mass spectrum
Current Medicinal Chemistry
Title: Identifying the Cellular Targets of Bioactive Small Molecules with Activity-Based Probes
Volume: 17 Issue: 27
Author(s): Xin Li and Yongzhou Hu
Affiliation:
Keywords: Target identification, phenotypic assay, activity-based probe, structure-activity relationship, radioisotope, biotin, fluorophore, mass spectrum
Abstract: The renaissance of cell- or organism-based phenotypic assays has made subsequent target identification for bioactive small organic molecules an important aspect of current drug discovery. Among the many strategies available for target identification, derivatizing bioactive small molecules into activity-based probes has the main advantage of determining small molecule-protein interactions directly in the native environment where the target proteins maintain their three-dimensional structures, including all the post-translational modifications, as the discrete small molecular probes usually have better access to intracellular compartments. Thus this chemical platform will not only afford a more precise means of understanding the mechanisms of action for bioactive molecules, but shed light onto the specificity of the bioactive small molecules. Here we will provide an overview of the strategies for the design of activity-based small molecular probes and review their applications for target identification using case studies. Special emphasis is placed on logistic concerns for probes design as well as recent developments in this field.
Export Options
About this article
Cite this article as:
Li Xin and Hu Yongzhou, Identifying the Cellular Targets of Bioactive Small Molecules with Activity-Based Probes, Current Medicinal Chemistry 2010; 17 (27) . https://dx.doi.org/10.2174/092986710791959747
DOI https://dx.doi.org/10.2174/092986710791959747 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Potential Interactions between miRNAs and Hypoxia: A New Layer in Cancer Hypoxia
Anti-Cancer Agents in Medicinal Chemistry Stemness or Not Stemness? Current Status and Perspectives of Adult Retinal Stem Cells
Current Stem Cell Research & Therapy Strategic Developments & Future Perspective on Gene Therapy for Breast Cancer: Role of mTOR and Brk/ PTK6 as Molecular Targets
Current Gene Therapy Basal Breast Cancer: A Complex and Deadly Molecular Subtype
Current Molecular Medicine Synthetic 2-Methoxyestradiol Derivatives: Structure-Activity Relationships
Current Medicinal Chemistry Gene Therapy Approaches for the Prevention of Restenosis
Current Vascular Pharmacology Discovery of BRM Targeted Therapies: Novel Reactivation of an Anticancer Gene
Letters in Drug Design & Discovery RNA Silencing: Recent Developments on miRNAs
Recent Patents on DNA & Gene Sequences Transfection of CXCR-4 Using Microbubble-Mediated Ultrasound Irradiation and Liposomes Improves the Migratory Ability of Bone Marrow Stromal Cells
Current Gene Therapy Prostate Cancer Molecular Background: The IGF-1Ec Story
Clinical Cancer Drugs A Comprehensive Overview of Colon Cancer- A Grim Reaper of the 21st Century
Current Medicinal Chemistry Neurokinin-1 Receptor Antagonists in Lung Cancer Therapy
Letters in Drug Design & Discovery DNA Methylation, An Epigenetic Mode of Gene Expression Regulation in Reproductive Science
Current Pharmaceutical Design Preclinical Studies of PROTACs in Hematological Malignancies
Cardiovascular & Hematological Disorders-Drug Targets Studies of p53 Tumor Suppression Activity in Mouse Models
Current Genomics Pharmacological Modulation of p53 Function in Cancer Therapy
Current Signal Transduction Therapy Tyrosine Kinase Receptor Transactivation Associated to G Protein-Coupled Receptors
Current Drug Targets Conditionally Replicating Adenoviruses for Cancer Treatment
Current Cancer Drug Targets Restoration of Chemoresistance Mechanism by Novel Drug Therapies in Breast Cancer Cell Lines
Current Drug Therapy Mechanisms Underlying Chemopreventive Effects of Flavonoids via Multiple Signaling Nodes within Nrf2-ARE and AhR-XRE Gene Regulatory Networks
Current Chemical Biology