Posters
« Back
Click Chemistry in Biomedical Applications
EP39488
Poster Title: Click Chemistry in Biomedical Applications
Submitted on 04 Nov 2022
Author(s): Sonia Li
Affiliations: Biopharma PEG Scientific Inc.
Poster Views: 199
View poster »


Poster Information
Abstract: The 2022 Nobel Prize in chemistry was awarded to scientists Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless for their development of click chemistry and bioorthogonal chemistry. [1]

nobel-chemistry-2022

Figure 1. 2022 Nobel Prize in chemistry, soucce: reference [1]

Barry Sharpless and Morten Meldal brought chemistry into the age of functionalism and laid the foundation for click chemistry. While Carolyn Bertozzi took click chemistry into a new dimension and began using it to map cells. Among many other applications, her bioorthogonal chemistry contributes to more targeted cancer therapies, such as antibody-drug conjugates (ADCs), fluorescent imaging, and targeted drug delivery, etc.

What Is Click Chemistry & Bioorthogonal Chemistry?
Click chemistry: A chemical synthesis method for the rapid and efficient synthesis of useful new molecules based on the heteroatom link (C-X-C). [1]

Bioorthogonal Chemistry: Chemical reactions that use the principles of click chemistry to occur inside of living systems without interfering with native biochemical processes.

In 2001, an examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds. The concept of "Click Chemistry" was inspired by the fact that nucleic acids, proteins and polysaccharides are condensed polymers held together by carbon-heteroatom bonds. Click chemistry is a chemical synthesis method that allows for the rapid and efficient synthesis of useful new molecules based on carbon-heteroatom link (C-X-C).

Prior to this, chemical synthesis was complicated and difficult but with low yields. Until the first generation of click chemistry, the monovalent copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was proposed, the complex reactions started to be simplified by building functional molecules in a patterned reaction manner. However, the cytotoxicity of copper catalysts limited the application of CuAAC reactions in vitro and in vivo.

Chemists have since discovered a strain-promoted alkyne-azide cycloaddition (SPAAC) reaction that allows the azide-alkyne reaction to occur without the need for a cytotoxic copper catalyst. This reaction has been used to label glycoproteins on the cell surface in vitro and in vivo with no apparent cytotoxicity.

However, some chemists were not satisfied with the second-order reaction rate constants of SPAAC. Therefore, Blackman et al. developed the inverse electron-demand Diels-Alder (iEDDA) reaction between the cycloaddition reactions of s-tetrazine and trans-cyclooctene (TCO) derivatives to produce faster copper-free click chemistry than the SPAAC reaction.
Summary: Click chemistry has made important advances in the field of biomedical research. In this article, we present several specific applications of click chemistry in biomedical research.References: [1] https://www.nobelprize.org/prizes/lists/all-nobel-prizes-in-chemistry/
[2] Kolb HC, Finn MG, Sharpless KB. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew Chem Int Ed Engl. 2001 Jun 1;40(11):2004-2021.
[3] Kim E, Koo H. Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo. Chem Sci. 2019 Aug 16;10(34):7835-7851.
[4] Vatansever EC, Kang J, Tuley A, Ward ES, Liu WR. An optimal "Click" formulation strategy for antibody-drug conjugate synthesis. Bioorg Med Chem. 2020 Dec 15;28(24):115808. doi: 10.1016/j.bmc.2020.115808.
[5]. Zammarchi F, Havenith KE, Chivers S, Hogg P, Bertelli F, et al. Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers. Mol Cancer Ther. 2022 Apr 1;21(4):582-593.
[6] Wurz RP, Dellamaggiore K, Dou H, Javier N, Lo MC, McCarter JD, Mohl D, Sastri C, Lipford JR, Cee VJ. A "Click Chemistry Platform" for the
Report abuse »
Questions
Ask the author a question about this poster.
Ask a Question »

Creative Commons