Glycobiology

Yesterday I heard a talk by Peter Seeberger about his research group at the Max Planck Institute for Colloids and Interfaces. That institute is based in Golm but through this event I discovered that in reality Seeberger’s group is at present housed in buildings belonging to the Free University in Dahlem. They will only move once a new extension to the building in Golm is ready. Seeberger’s speciality is the synthesis of complex sugars from monosaccharides. After the talk there was a guided tour of the laboratories and we saw a machine for the synthesis of peptides. In that group it is actually being used to make other types of polymers. If it was being used for peptide synthesis it would just be possible to type in the sequence of the desired peptide and press a button. (Maybe I am oversimplifying here but we were told that almost anyone could use the machine, without any special knowledge of chemistry.) Seeberger’s speciality is an analogous machine for the much more difficult task of making polysaccharides with any desired structure.

This has important applications to biology. For instance, cells are decorated with various glycoproteins, glycolipids and other compounds containing sugars on their surfaces. They are important for the recognition of cells and for the entry of pathogens. As a consequence it is easy to see that antibodies against sugars should be important for biology and medicine. In the talk it was mentioned that certian harmful effects of the malaria pathogen are due to a toxin that it produces and that this toxin is a polysaccharide. In endemic areas many people, in particular children, are apparently healthy despite high loads of the parasite in their blood. The explanation for this is that they have antibodies against the toxin. Neutralizing the toxin removes the most serious (and possibly fatal) effects of the pathogen although the organism remains plentiful. It was explained that the immune system of small children cannot recognize sugars so that they may die before they can develop this protection. A possible treatment is to give them a kind of vaccine to raise these antibodies. A substance developed by Seeberger is at an advanced stage of preclinical testing. He also said that vaccines based on polysaccharides are less likely to be met by resistance than more conventional ones based on peptides since the process of producing sugars in cells is so much more indirect than the that of transcription and translation leading from DNA to protein.

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