Abstract
The first reported click reaction, copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition had limited biocompatibility due to the high toxicity of copper. Since alternative bioorthogonal click reactions have been developed, they have strongly influenced the field of chemical biology. Here are summarized three main metal-free click methodologies based on cycloaddition, Staudinger and thioene reactions. This review contains the basic principles, some mechanistic considerations and a collection of reagents that can be used in each method. Firstly, Diels-Alder and strain promoted inverse electron demand Diels-Alder cycloadditions are outlined together with triazole and isoxazole formation by 1,3-dipolar cycloadditions. Secondly, Staudinger-Bertozzi ligation, a chemoselective reaction of azides and engineered triarylphosphines, is discussed. Finally, thio-click chemistries including thiol-ene, thiol-yne, thio-Michael and fluoro-thioclick reactions are reviewed. Among the most important bioapplications of these click methodologies is the labeling of glycans, proteins, lipids and DNA. Additionally, synthetic methods and surface immobilization of biomolecules and biologically useful polymeric materials are also reviewed.
Keywords: Biological applications, Bioorthogonal chemistry, Click chemistry, Cycloadditions, Staudinger-Bertozzi ligation, Thio-click chemistry
Current Organic Chemistry
Title:Application of Metal Free Click Chemistry in Biological Studies
Volume: 17 Issue: 6
Author(s): Pavels Ostrovskis, Chandra M. R. Volla, Maris Turks and Dean Markovic
Affiliation:
Keywords: Biological applications, Bioorthogonal chemistry, Click chemistry, Cycloadditions, Staudinger-Bertozzi ligation, Thio-click chemistry
Abstract: The first reported click reaction, copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition had limited biocompatibility due to the high toxicity of copper. Since alternative bioorthogonal click reactions have been developed, they have strongly influenced the field of chemical biology. Here are summarized three main metal-free click methodologies based on cycloaddition, Staudinger and thioene reactions. This review contains the basic principles, some mechanistic considerations and a collection of reagents that can be used in each method. Firstly, Diels-Alder and strain promoted inverse electron demand Diels-Alder cycloadditions are outlined together with triazole and isoxazole formation by 1,3-dipolar cycloadditions. Secondly, Staudinger-Bertozzi ligation, a chemoselective reaction of azides and engineered triarylphosphines, is discussed. Finally, thio-click chemistries including thiol-ene, thiol-yne, thio-Michael and fluoro-thioclick reactions are reviewed. Among the most important bioapplications of these click methodologies is the labeling of glycans, proteins, lipids and DNA. Additionally, synthetic methods and surface immobilization of biomolecules and biologically useful polymeric materials are also reviewed.
Export Options
About this article
Cite this article as:
Ostrovskis Pavels, M. R. Volla Chandra, Turks Maris and Markovic Dean, Application of Metal Free Click Chemistry in Biological Studies, Current Organic Chemistry 2013; 17 (6) . https://dx.doi.org/10.2174/1385272811317060006
DOI https://dx.doi.org/10.2174/1385272811317060006 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
Call for Papers in Thematic Issues
Advances of Heterocyclic Chemistry with Pesticide Activity
Global food safety and security will continue to be a global concern for the next 50 years and beyond. Plant diseases have had a significant impact on food safety and security throughout the entire food chain, from primary production to consumption. While conventional chemical pesticides have been traditionally used for ...read more
Calculation design of covalent/metal organic framework based catalysts
This research area combines theoretical computation and screening with machine learning for the design of covalent/metal organic framework-based catalysts, bridging the disciplines of organic chemistry, physical chemistry, computational chemistry, materials science, and machine learning. It covers several critical aspects: designing and synthesizing organic catalysts for improved performance, applying computational methods ...read more
Carbohydrates conversion in biofuels and bioproducts
Biomass pretreatment, hydrolysis, and saccharification of carbohydrates, and sugars bioconversion in biofuels and bioproducts within a biorefinery framework. Carbohydrates derived from woody biomass, agricultural wastes, algae, sewage sludge, or any other lignocellulosic feedstock are included in this issue. Simulation, techno-economic analysis, and life cycle analysis of a biorefinery process are ...read more
Catalytic C-H bond activation as a tool for functionalization of heterocycles
The major topic is the functionalization of heterocycles through catalyzed C-H bond activation. The strategies based on C-H activation not only provide straightforward formation of C-C or C-X bonds but, more importantly, allow for the avoidance of pre-functionalization of one or two of the cross-coupling partners. The beneficial impact of ...read more
Related Journals
- 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
-
Multi-Target Inhibitors for Proteins Associated with Alzheimer: In Silico Discovery using Fragment-Based Descriptors
Current Alzheimer Research Identification of N- and C-Terminal Residues Involved in MAP Kinase Phosphatase 3 (MKP3) Interdomain Binding and Auto-Inhibition
Protein & Peptide Letters Bladder Cancer: Molecular Determinants of Personalized Therapy
Current Drug Targets Interplay between Catalysts and Substrates for Activity of Class Ib Aminoacyl-tRNA Synthetases and Implications for Pharmacology
Current Topics in Medicinal Chemistry Structural Heterogeneity and Multifunctionality of Lactoferrin
Current Protein & Peptide Science Amylopectin-like Starch is Present in the Cell Walls of Kiwifruit Pericarp Tissues during Development
The Natural Products Journal Herpes Simplex Encephalitis: From Virus to Therapy
Infectious Disorders - Drug Targets Structure-Based Hybridization, Conventional and Microwave Irradiated Synthesis, Biological Evaluation and Molecular Docking Studies of New Compounds Derived from Thiomorpholin
Letters in Drug Design & Discovery Aqueous Enzymatic Extraction of Oil from Microwave-pretreated Jicaro Seeds
Current Biochemical Engineering (Discontinued) Thermal Stability and Phase Transitions in WO<sub>3</sub>-ZrO<sub>2</sub> and WO<sub>3</sub>-TiO<sub>2</sub> Composites
Innovations in Corrosion and Materials Science (Discontinued) Proteomics of Human Pulmonary Surfactant Proteins
Current Proteomics A Simple Approach to DC-Cholesterol, its Analogues and Vitamin D-Based Cationic Lipids for Gene Therapy
Letters in Organic Chemistry New Perspectives on Acyl Glucuronide Risk Assessment in Drug Discovery: Investigation of In vitro Stability, In situ Reactivity, and Bioactivation
Drug Metabolism Letters Polymer Structures for Sensors and Actuators 1. Analyte Biosensor
Recent Patents on Materials Science Deciphering Signaling Control by Phosphoproteome Using Mass Spectrometry
Protein & Peptide Letters The Role of Atomic Spectrometric Techniques in the Determination of Chemical Elements in Atmospheric Aerosols
Current Analytical Chemistry Pharmaceutical Applications of the Benzylisoquinoline Alkaloids from Argemone mexicana L.
Current Topics in Medicinal Chemistry Last Decade of Research in Sonochemistry for Green Organic Synthesis
Recent Patents on Chemical Engineering The Role of Hesperidin in Cell Signal Transduction Pathway for the Prevention or Treatment of Cancer
Current Medicinal Chemistry Cytokines in Human Breast Milk: Immunological Significance for Newborns
Current Nutrition & Food Science