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!!!