CLICK CHEMISTRY
By: Yeshitila Asteraye Tsigie (PhD Student)National Taiwan University of Science and Technology
Click Chemistry & Its Role in
Biomolecular Engineering
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Contents
Introduction Click Chemistry Applications of Click Chemistry Conclusions
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Introduction
Nobel Prize in Chemistry and introducing the concept “Click Chemistry” ??????????????.
2001 K.B. Sharpless
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Introduction (Cont…)
Functional Groups sites of chemical reactivity in an organic
compound
Biomolecules Organic building blocks of organisms
Some Important Terms
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Introduction (Cont…)
Nature generates substances by joining small molecular units.
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Is it possible to generate larger molecules from small molecules in the laboratory?
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Click Chemistry
describes chemical reactions that generate substances quickly, reliably and in quantitative yield by joining small building blocks under mild conditions.
is inspired by the fact that chemical reactions in nature also generate substances by joining small molecular units.
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Click Chemistry (Cont…)
a new way of thinking molecular construction.
is based on the use of fast and efficient reactions between building blocks
permits the construction of highly diversified structures through the use of reactive subunits.
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Why Click Chemistry is different from chemistry of native biomolecules????
•It is very selective • only between azide and alkyne components.• It is does not interfere with most any other organic
groups present in DNA and proteins being labeled, such as amino and carboxy groups.
•There are no azides and alkynes in native biomolecules. • These groups should be specially introduced into DNA and
proteins. •Click Chemistry takes place in water.
• Aqueous DMSO, DMF, acetonitrile, alcohols, or pure water and buffers can be used for the reaction.
• The reaction is biocompatible and can take place in living cells.
•Reaction is quick and quantitative. •The reaction is pH-insensitive.
• no need to control pH in reaction mixture. • works well in pH interval of 4-11.
•Most click reactions involve the formation of carbon–heteroatom (mostly N, O, and S) bonds.
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Why Azide and Alkyne Groups? built-in high energy content ‘invisible’ in all terrestrial
environments but, when properly introduced,
they ‘click’ forming an indestructible triazole link
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Reactions in Click Chemistry
Nucleophilic substitutions
Electrophilic substitutions
Ring opening
. Cycloadditions reactions such as the copper (I)-modified Huisgen reaction. Diels-Alder reaction
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Huisgen’s [1,3] Dipolar Cycloaddition
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CuAAC - Cu catalyzed alkyne azide cycloaddition (CuAAC Ligation)
The most popular reaction which fulfills “click reaction”
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Mechanism of CuAAC Click Reaction
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Applications of Click Chemistry
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Synthesis of N-Terminally Linked Protein Dimers and Trimers
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Copper-free click chemistry in living animals
To label azidosugars
www.pnas.org/cgi/doi/10.1073/pnas.0911116107
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To prepare functionalized poly(alkyl cyanoacrylate) nanoparticles
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Preparation of Covalently Stabilized Thermoresponsive Microcapsules layer-by-layer
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Preparation of Sliding Supramolecular Polymer Brushes (SSPBs)
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Assembling Ferromagnetic FePt Nano-particles as SAM
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Site-Selective Functionalization of a TubularlyAssembled Hexabenzocoronene
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Bioconjugated Janus Particles preparation
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Dendrimer Synthesis
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Labelling oligonucleotides with carbohydrates
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Functionalization of Gold Nanoparticles and Linking to Lipase
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Conclusions
Click Chemistry Newly emerging field of chemistry Aqueous environment Selective and specific Fast Efficient Used for synthesizing biologically
important compounds Is based on nature’s principle of producing
macromolecules from small building blocks
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Thank You For Your Attention!!!