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News — A research team from the Department of Chemistry at the University of Montreal has just developed new tools to study the encounter between the members of two families of biomolecules essential to life: sugars and proteins. Opening the way to numerous applications, this work has just been published in  , a renowned scientific journal in chemistry.

Sugars, omnipresent in biology

“Caramels, candies and chocolates”…, sugar is omnipresent in our lives, but not only in the sense that most people understand it. Indeed, in the large families of the living world, carbohydrates go well beyond our dietary pleasures and include an immense diversity of natural biomolecules.

“All the cells making up our world are covered in sugar and this is true for all living organisms. These carbohydrates are therefore on the front line in almost all biological processes and play fundamental roles in maintaining the health of our body or triggering certain diseases,” argues Samy Cecioni, professor in the Department of Chemistry at UdeM.

He continues: “Scientists have long thought that these complex sugars were simple decorations on the cell. We now know that sugars interact with many other molecules, notably with lectins, a large family of proteins.”

Sugars, lectins, bacteria, viruses and cancer cells

Lectins, sometimes also called “hemagglutinins”, are natural proteins present in all living organisms and which have the particularity of recognizing sugars and attaching to them temporarily.

This specific and reversible recognition of carbohydrates is involved in various biological processes, such as recognition between cells in immune responses triggered by infection.

Lectin research is a booming field. Scientists have discovered that lectins “stick” to sugars… and this union plays a role in the onset of many diseases.

“The more we study this phenomenon between sugars and lectins, the more we realize its essential importance in biology. Several studies have shown that from the bacteria that colonize our lungs, from the flu virus that sticks to our cells to trigger an infection to the cancer cells that trick our immune system to avoid being destroyed, it is each time the “story of an encounter between lectins and sugars”, summarizes Samy Cecioni.

Sugars and lectins: a stealthy, low-intensity encounter

However, several pieces are missing from the puzzle to understand how the union takes place, since it is not easy to detect when a sugar will bind to some of these lectins.

These interactions are generally furtive and low intensity. Cécile Bousch, a master's student in Professor Cecioni's laboratory, and her doctoral colleague Brandon Vreulz had the idea of ​​using light to illuminate these interactions. With their professor, they created a sort of chemical probe capable of “freezing” the interaction between a sugar and a lectin in an irreversible manner while making it fluorescent.

The image of a key-lock model is often used in popular science to describe how biomolecules interact. To be able to study this biochemical encounter, chemists had already designed molecules capable of forming new chemical bonds to block the key (the sugar) in the lock (the lectin) and therefore discover which sugars linked with lectins important for health .

The idea of ​​Professor Cecioni's team was to attach a reactive chromophore – a group of atoms which gives color to a molecule – to the sugar so that it, when it binds to a lectin, can activate its fluorescent “key” function. Once the protein is captured and fluoresces, it becomes much easier for scientists to study the underlying mechanisms and their disruptions.

Professor Cecioni and his students are confident that the technology they have developed could be used with other types of molecules. We could even control the color of the new responsive keys that would be created. By making it possible to visualize interactions between molecules, this discovery extends our collection of tools for the study of biological interactions and could color our very incomplete vision of sugar recognition.

About this study

The article “  ”, by Cécile Bousch and colleagues, was published on October 17, 2023 in Angewandte Chemie.

This study was funded by the Natural Sciences and Engineering Research Council of Canada, the Fonds de recherche du Québec – Nature et technologies and the Canada Foundation for Innovation.

About Professor Samy Cecioni

Recruited by the Department of Chemistry in 2019,  is a young researcher who specializes in the emerging fields of biological chemistry and glycomics. He is the recipient of one of the 2021 research excellence medals from the Faculty of Arts and Sciences of UdeM.

“Our research team is developing new tools to accelerate discoveries in the field of glycosciences. The set of molecules modified by sugars is sometimes described as the “dark matter” of life and we propose multidisciplinary approaches at the intersection of chemistry and biology to enable advances relevant to human health,” he says. To find out more,  Professor Cecioni explain the research carried out in his laboratory.