Sugars on human cells play a crucial role in regulating various biological processes. Irregular sugar expression is linked to diseases like cancer, where specific sugars on cancer cells contribute to immune evasion, metastasis, proliferation, and resistance to therapies. Targeting these cancer-specific sugars in preclinical models presents a promising avenue for new cancer therapies, emphasizing the need for a deeper understanding to develop effective medicines. Glycosylation reactions have been challenging to control due to the formation of two stereoisomers, making prediction difficult.
Making new molecules is important in the chemical and pharmaceutical industries. New molecules are made by chemical reactions. Often it takes multiple reaction steps to make a new molecule. Selecting the chemical reactions required to give the desired molecule are essential. Understanding the reactivity of our starting molecules will help researchers to predict and design their synthesis routes towards their desired product.
In his master project, De Kleijne developed a novel method to detect normally "invisible" reaction intermediates. By establishing a chemical equilibrium between the invisible and a stable visible intermediate, he used exchange NMR to identify previously unknown glycosylation reaction intermediates. The project that was awarded with the KHMW young talent graduation award was about the detection and characterization of glycosyl dioxanium ions in solution using NMR spectroscopy. For this research the De Kleijne worked in close collaboration with dr. Paul White who runs the synthetic organic NMR department. "We applied advanced NMR techniques to detect ‘invisible’ reaction intermediates. Basically what we did is take a chemical reaction, but it in front of a photo camera for molecules (the NMR) and take pictures while the chemical reaction is going on", De Kleijne explains.
The research project has given new insight in the reactivity of our studied molecule which likely applies for other molecules too. Knowledge of this reactivity can therefore aid researchers to design their synthesis and make other new molecules in an efficient way. This innovative approach is not only applicable to glycosylation but also to other types of reactions. "I was quite surprised that I won an award, I was honoured that, on national level, my internship thesis was this good. I just had fun in the lab, working on the project; working with Thomas, Paul, Sam, and Hidde; and I had fun with the rest of the research group. I never would have expected this", De Kleijne says.
Synthetic Organic Chemistry
De Kleijne did his master under supervision of Thomas Boltje in the Synthetic Organic Chemistry department of IMM. They study and identifies important glycans involved in malignant transformations and pathogenic infection and they develop chemical tools. The Boltje group is part of the Synthetic Organic Chemistry group from prof. Floris Rutjes, which focuses on the design and synthesis of biologically relevant molecules and improve existing methods of synthesis.
As the oldest learned society in the Netherlands, the Royal Holland Society of Sciences and Humanities (KHMW) acts as an effective meeting place for leading figures in academia and beyond. Awards and scholarships are made possible through donations from companies, foundations, funds, and societies.
The award ceremony will take place on November 27th, 2023.
We warmly congratulate Frank with this prize.