Glycobiotechnology

Glycobiotechnology - Sugar research is picking up speed

Alongside DNA and proteins, sugar structures play an important role in cellular transport and communication processes. They are also part of the molecular control and regulation machinery making them of particular interest to biotechnologists. The pharmaceutical industry, as well as the food sector and material sciences, have realised the potential of sugar structures.

The era of sugar research is dawning; in fact, it has already begun. Approximately ten to fifteen years ago, life scientists started to rethink the role of sugar structures. Better analytical methods and a growing and deeper understanding of cellular mechanisms revealed that sugar structures had far more biological functions than previously thought. As a result, sugar research has received greater attention in recent years. In 2003, the Massachusetts Institute of Technology (MIT) rated glycobiotechnology as one of the top ten technologies of the future.

Both basic and applied research are being carried out in Germany in order to turn glycobiology and glycobiotechnology into a field of excellence for German research and to become a world leader in this field. Following the “Glycobiotechnology Funding Priority”, the BMBF launched the “Glycobiotechnology Workgroup Contest” in 2006 in order to establish this area of research in Germany.

Cellular sugar structures are the models for new materials and surfaces

Saccharose (Photo: Takeda Pharma)

Baden-Württemberg has excellent researchers and projects in the field of glycobiology. One of the major priorities is an investigation into the cells' sugar coat. A workgroup, headed by Dr. Ralf Richter at the Stuttgart Max Planck Institute, is investigating and developing models of the cells' sugar coat. The researchers are hoping to gain insights into structure-function relationships and develop the system into a new biosensoric platform (see article entitled "How do cells work? Glycoconjugate cell coat models provide new answers").

The knowledge of sugars and their binding partners is essential for the development of innovative biomaterials. This concerns implants, prostheses and, in general, all materials that interact with biological systems. Sugar-binding proteins, the lectins, are the focus of many research activities. For example, Prof. Dr. Wittmann of the University of Constance carries out research on the multivalent recognition and differentiation of galactose-binding lectins through surface-bound neoglycopeptides (see article entitled: “How cells communicate. Constance chemists are investigating carbohydrate-protein interactions”).

Binding behaviour offers new perspectives for diagnosis and therapy

A natural killer cell (Photo: Prof. Dr. Rupert Handgretinger)

The specific binding of lectins to sugar structures is also a key process for medicine in which it is hoped that further insights into this process will lead to completely new therapies. Dr. Ingo Müller’s research team at the University of Tübingen is working on the specific sugar coat of cancer cells and is investigating how the sugars interact with the surface lectins of immune system cells (see article entitled "Cancer cells: glycosylation pattern as potential target for intervention").

The principle of specific bindings between sugars and proteins is also used in biotechnological drug production. Intensive research is devoted to developing new and optimised cell systems that enable the binding of sugars to therapeutic molecules. Freiburg-based greenovation Biotech GmbH is one such example. The company uses moss plants to develop therapeutic proteins that are combined with human sugar structures so that the target cells in the human body are able to recognise the therapeutic proteins.

In 1985, Boehringer Ingelheim’s first biopharmaceutical, Actilyse, was a glycoprotein. Dr. Michael Schlüter, who has been involved in this field since the beginning, is the head of a department that has grown considerably over the years - as has the production of biopharmaceuticals in Biberach, Germany.

Food with bioactive sugar compounds

Fucus species are also suitable as suppliers of algal polysaccharides. (Photo: Anoxymer GmbH)

Esslingen-based Anoxymer GmbH, has taken a different route, though it is also based on plants. The company investigates the health benefits of plant-derived sugar structures that are consumed with the food we eat. It develops extracts enriched with bioactive polysaccharides. The article “More than just empty calories – polysaccharides in food” deals with the therapeutic and preventive benefits of sugars.

All glycobiological and glycobiotechnological questions have something in common: the research on these highly-complex sugar molecules is always associated with large amounts of data. These data have to be compiled, administered and processed. Computer-assisted simulations and modeling in the field of glycobiology can only be dealt with using modern bioinformatics methods due to particularly complex relationships. Dr. Claus-Wilhelm von der Lieth of the German Cancer Research Centre (DKFZ) in Heidelberg was a pioneer of glycobioinformatics. His activities are dealt with in the article entitled “Glycobiotechnology: breakthrough for glycomics”.

What is glycobio(techno)logy?

Complex sugar compounds are known as glycans. The word is derived from Greek glykós, which means ‘sweet’. Glycans consist of individual sugar components (monomers) such as glucose or fructose that are combined to form polymers. These chains can be very long, be branched or be connected with other molecules such as lipids or proteins. This leads to a complexity that is far greater than that of pure nucleic acids and proteins. Three sugar monomers are sufficient to produce more than 27,000 different structures. This also leads to a huge variety of functions: Glycans are important for the communication between cells or between cells and their molecular environment; they are also important for tissue structure and the storing of information.

The terms proteome or genome refer to all proteins or genes of an organism. Similarly, glycome is the entire complement of sugars. Glycomics is often used synonymously with the term glycobiology.

Glycobiology is the study of the structure and function of saccharides (sugar chains or glycans); glycobiotechnology focuses on their practical use. In medicine, cell- and disease-specific glycans can serve as diagnostic markers or as targets for drug therapies. In addition, sugar chains play an increasing role in biopharmaceuticals, in which they can affect stability, activity and immunogenicity of drugs. Glycans have also given new ideas to material scientists, where they can serve as a model for the development of new biomaterials such as scaffolds for the cultivation of artificial tissue (tissue engineering). Last but not least, as food additives, sugars can also have a beneficial effect on human health.

leh - 01.02.2008
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