Click chemistry and bio-orthogonal chemistry hit the headlines last week (w/c 3 Oct 2022) when the 2022 Nobel Prize in Chemistry was jointly awarded to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless.
The press release states that: “The Nobel Prize in Chemistry 2022 is about making difficult processes easier. Barry Sharpless and Morten Meldal have laid the foundation for a functional form of chemistry – click chemistry – in which molecular building blocks snap together quickly and efficiently. Carolyn Bertozzi has taken click chemistry to a new dimension and started utilizing it in living organisms.”
The news was of particular interest to Charnwood Discovery scientists Dr Ngoc (Ruby) Nguyen and Dr Matthew Allen who were happy to reflect on and share their own experiences of using click chemistry and bio-orthogonal chemistry.
Ngoc was curious about the application of click chemistry in biological systems and wanted to explore it further. This prompted Ngoc to apply for a position as Research Fellow in Chemical Biology at Strathclyde University. There she focused on the synthesis of fluorogens to develop RNA aptamers, exploration of copper free click chemistry, and application of click chemistry in tagging and imaging.
“The project I worked on was to develop the ‘Next-generation bio-orthogonal reaction platform for RNA tagging and imaging’. Our objectives were to synthesise fluorogens and their precursors to develop RNA aptamers – utilising aptamers as “click aptazymes”. We also wanted to explore copper free click chemistry for ynamines and utilise click chemistry in the development of FRET pairs.”
Ngoc went on to explain that there was very complex chemistry involved in the project and that Charnwood Discovery actually provided two custom synthesis compounds for the project as it needed specific knowledge and experience to synthesize them.
“I learnt so much from working on this project and I look forward to applying this knowledge in the future as a Senior Research Chemist I at Charnwood Discovery.”
Dr Ngoc (Ruby) Nguyen
Dr Ngoc (Ruby) Nguyen has a PhD in Medicinal Chemistry with degrees in Pharmacology (MSc) and Pharmacy (BSc).
Having gained practical skills in a wide range of chemistry related subjects during her undergraduate degree, Ngoc worked as a medical sales representative, gaining vital industry and commercial experience.
However, her enthusiasm for organic synthesis and a desire to further her career in drug discovery eventually brought her to Charnwood Discovery.
Ngoc brings her skills in organic synthetic chemistry, docking, molecular dynamics simulations, plus bio-orthogonal chemistry to client projects.
Purification Scientist Matt Allen had an early introduction to click chemistry through his PhD and subsequent thesis on the ‘Development of Tools for Glycan Analysis and Quantitative Sialic Acid Glycomics’.
Matt explains that his research on glycans sought a different approach to overcome the inherent structures of glycans that hinder their detection by traditional methods. “Analyzing glycans is quite a challenge as they are analytically very difficult – for example they can’t be detected by UV or mass spectrometry. They are so important though for finding and understanding disease states so to be able to see them we must derivatize them.”
A molecule was created that could be clicked after the glycan had been labelled which proved to be the same chromatographically as the parent compound. The benefit was greater detection capability and wider uses of glycan.
“Once these labels have been added, glycans lack many further uses. Creating labels that can undergo a click reaction allows us to do reactions that doesn’t cause modification to the glycan which may lose information, while also giving us the ability to do more analysis with it”.
“It was an immensely satisfying research project as glycans are so important for the various roles they play including biotherapeutic efficacy and structural functions. The opportunity to apply click chemistry was very welcome and I took a lot from this experience.”
Dr Matthew Allen
Dr Matt Allen has a PhD in Chemical Biology, with an MSc in Chemistry for Drug Discovery and a BSc in Chemistry.
After completing his PhD Matt joined Charnwood Discovery as a Purification Scientist in the analytical team.
Matt’s synthetic chemistry experience along with skills in HPLC, NMR, UV/Vis Spectroscopy, amongst others, ensures that he is well placed to support colleagues with their separation and purification requirements.
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