1. Click Chemistry Click Chemistry & Its Role in Biomolecular Engineering By: Yeshitila Asteraye Tsigie (PhD Student) National Taiwan University of Science and Technology

2. Contents Introduction Click Chemistry Applications of Click Chemistry Conclusions 2

3. Introduction K.B. Sharpless 2001 Nobel Prize in Chemistry and introducing the concept “Click Chemistry” ??????????????. 3

4. Introduction (Cont…) Some Important Terms Functional Groups sites of chemical reactivity in an organic compound Biomolecules Organic building blocks of organisms 4

5. Introduction (Cont…) Nature generates substances by joining small molecular units. 5

6. 6

7. Is it possible to generate larger molecules from small molecules in the laboratory? 7

8. 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. 8

9. 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. 9

11. only between azide and alkyne components.

12. It is does not interfere with most any other organic groups present in DNA and proteins being labeled, such as amino and carboxy groups.

13. There are no azides and alkynes in native biomolecules.

14. These groups should be specially introduced into DNA and proteins.

15. Click Chemistry takes place in water.

16. Aqueous DMSO, DMF, acetonitrile, alcohols, or pure water and buffers can be used for the reaction.

17. The reaction is biocompatible and can take place in living cells.

18. Reaction is quick and quantitative.

19. The reaction is pH-insensitive.

20. no need to control pH in reaction mixture.

21. works well in pH interval of 4-11.

22. Most click reactions involve the formation of carbon–heteroatom (mostly N, O, and S) bonds.10

23. WhyAzide and Alkyne Groups? built-in high energy content ‘invisible’ in all terrestrial environments but, when properly introduced, they ‘click’ forming an indestructible triazolelink 11

24. Reactions in Click Chemistry Nucleophilic substitutions Electrophilic substitutions Ring opening . Cycloadditions reactions such as the copper (I)-modified Huisgen reaction . Diels-Alder reaction 12

25. Huisgen’s [1,3] Dipolar Cycloaddition 13

26. CuAAC - Cu catalyzed alkyneazidecycloaddition (CuAAC Ligation) The most popular reaction which fulfills “click reaction” 14

27. Mechanism of CuAAC Click Reaction 15

28. Applications of Click Chemistry 16

29. Synthesis of N-Terminally Linked Protein Dimers and Trimers 17

30. Copper-free click chemistry in living animals To label azidosugars www.pnas.org/cgi/doi/10.1073/pnas.0911116107 18

31. To prepare functionalized poly(alkyl cyanoacrylate) nanoparticles 19

32. Preparation of Covalently Stabilized Thermoresponsive Microcapsules layer-by-layer 20

33. Preparation of Sliding Supramolecular Polymer Brushes (SSPBs) 21

34. Assembling Ferromagnetic FePtNano-particles as SAM 22

35. Site-Selective Functionalization of a TubularlyAssembled Hexabenzocoronene 23

36. Bioconjugated Janus Particles preparation 24

37. Dendrimer Synthesis 25

38. Labellingoligonucleotides with carbohydrates 26

39. Functionalization of Gold Nanoparticles and Linking to Lipase 27

40. 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 28

41. 29 Thank You For Your Attention!!!