The Click Chemistry used in GlyCLICK® is Awarded the Nobel Prize!
Every autumn, the Royal Swedish Academy of Sciences announces the winners of the prestigious Nobel Prize. This year’s Chemistry Prize goes to Carolyn Bertozzi, Barry Sharpless and Morten Meldal for the development of click chemistry and bioorthogonal chemistry. Click chemistry is a fundamental part of our GlyCLICK technology. By combining Fc glycan remodeling and the award-winning click chemistry, GlyCLICK enables site-specific labeling of antibodies!
The Nobel Prize in Chemistry 2022 is about finding new chemical ideals and make difficult processes easier. We are very happy and proud to be able to offer a Nobel Prize-winning click chemistry technology in a kit format for site-specific labeling of IgG!
What is click chemistry, and what findings led to the Nobel Prize?
The concept of click chemistry was first coined by Barry Sharpless in the early 00’s1. Shortly after that, Sharpless and Morten Meldal, independently of each other, presented what is today considered the crown jewel of click chemistry, the copper catalyzed azide-alkyne cycloaddition (CuAAC)2,3. The CuAAC technology is based on the finding that when copper is present as a catalyst, alkyne and the chemical group azide click together and form a stable ring-shaped structure called a triazole. Among other applications, the CuAAC technology is today widely used in the development of pharmaceuticals and for mapping DNA.
Carolyn Bertozzi took the click chemistry concept to a new level by making the technology applicable to biological systems. She wanted to use click chemistry to make it easier to map glycans. However, since the toxicity of copper ions limited its use in living organisms, an alternative solution was needed. In the literature it had been shown that azides and alkynes can react without the help of copper, if the alkyne is forced into a ring-shaped chemical structure. Bertozzi found this type of reaction to work well in living cells, and the copper-free strain-promoted alkyne-azide cycloaddition (SPAAC) click reaction was born4.
How is this coupled to the GlyCLICK technology offered by Genovis?
1. GlyCLICK is a three-step site-specific labeling technology for IgG, where the Fc-specific endoglycosidase GlycINATOR® first hydrolyzes the Fc glycans to the innermost GlcNAc of IgG.
2. Azide-containing UDP-GalNAz is then enzymatically attached to the exposed GlcNAc to generate an azide-activated antibody that is reactive with an alkyne-carrying label.
3. The azide-activated antibody can then be conjugated with any label of choice through the award-winning click chemistry reaction SPAAC.
Available GlyCLICK formats
We offer GlyCLICK in kits for the site-specific labeling (DOL = 2) of a range of labels to IgG, including fluorophores, DFO and biotin for imaging and immunoassays. We also offer kits for the development of antibody-drug conjugates (ADCs). With the GlyCLICK Azide Activation kit, an azide-activated antibody is generated for conjugation with any alkyne-carrying label of choice.
Available GlyCLICK formats; GlyCLICK Fluorophore, Biotin, DFO, ADC and Azide Activation.
Oh, and while we’re clicking! Our TransGLYCIT Azide Activation technology can also be used to create an antibody eligible for click chemistry! This technology is also site-specific, but instead of a DOL of 2, TransGLYCIT Azide Activation generates antibodies with a DOL of 4.
TransGLYCIT Azide Activation.
We send our warmest congratulations to Carolyn Bertozzi, Barry Sharpless and Morten Meldal for being awarded the Nobel Prize in Chemistry 2022!
“Click chemistry and bioorthogonal reactions have taken chemistry into the era of functionalism. This is bringing the greatest benefit to humankind.”
– Press Release, The Nobel Prize in Chemistry 2022, https://www.nobelprize.org/prizes/chemistry/2022/press-release/
References
1. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem. Int. Ed. 2001, 40 (11), 2004–2021.
2. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem. Int. Ed. 2002, 41 (14), 2596–2599.
3. Tornøe, C. W.; Meldal, M. Peptidotriazoles: Copper(I)-Catalysed 1,3-Dipolar Cycloadditions on Solid Phase. In Peptides 2001, proc. Am. Pept. symp.; American Peptide Society; American Peptide Society; Kluwer Academic Publishers: San Diego, 2001; pp 263–264.
4. Agard, N. J.; Prescher, J. A.; Bertozzi, C. R. A Strain-Promoted [3 + 2] Azide−alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems. J. Am. Chem. Soc. 2004, 126 (46), 15046–15047.