Research and Development Support Agency
(Agentúra na podporu výskumu a vývoja)

APVV-51-040205

Oligosaccharides, neoglyco-peptides/proteins and humanized plastics – their synthesis and applications

Project supported by the Slovak Research and Development Agency under contract no. APVV-51-040205

Principal investigator:
Dr. Jozef Nahalka
Tel: +421 2 59410319
FAX: +421 2 59410222
E-mail: nahalka@savba.sk

The past three decades have seen enormous stride in decoding the biorecognition information conserved in branched oligosaccharide structures and applying the information in pharmaceutical development. Neoglyco-peptides/proteins/plastics can be synthesized by either chemical or enzymatic ways, which both have their advantages and disadvantages. Chemical synthesis can introduce some unnatural oligosaccharides, while enzymatic approach is more suited to tailor the complicated oligosaccharides on glyco-polymers. For example, recombinant yeast fermentation technology, as in vivo enzymatic approach, provides standardized glycoprotein libraries, and these glycoproteins can be further tailored in vitro to final design by “cheap and stable” automated (enzymatic) sugar synthesis. Carbohydrate vaccines have been the main focus of glycotechnology research in recent years. But there is a lot of exciting technology possibilities in the field of carbohydrate scientists. This project is focused on the glycotargeting of microbial cells and enveloped viruses by glycosylated antibiotics, blocking of host – viral / host – bacterial interaction by biospecific neoglycoproteins, and humanization of synthetic implant surface by biospecific glycocore.

Group members: Jozef Nahálka, PhD
Peter Gemeiner, DSc
Mislovičová Danica, PhD
Vikartovská Alica, PhD
Masárová Jana, PhD
Pätoprstý Vladimír, PhD
Klaudiny Jaroslav, PhD
Kovárová Anna-Maria, MSc
Hrabárová Eva, MSc

Publications:
1. Nahálka, J., Mislovičová, D. & Kavcová, H. 2009, "Targeting lectin activity into inclusion bodies for the chracterisation of glycoproteins", Molecular BioSystems, DOI: 10.1039/b900526a
2. Nahálka, J. & Pätoprstý, V. 2009, "Enzymatic synthesis of sialylation substrates powered by a novel polyphosphate kinase (PPK3)", Organic and Biomolecular Chemistry, vol. 7, no. 9, pp. 1778-1780.
3. Mislovičová, D., Turjan, J., Vikartovská, A. & Pätoprstý, V. 2009, "Removal of d-glucose from a mixture with d-mannose using immobilized glucose oxidase", Journal of Molecular Catalysis B: Enzymatic, vol. 60, no. 1-2, pp. 45-49.
4. Nahálka, J., Vikartovská, A. & Hrabárová, E. 2008, "A crosslinked inclusion body process for sialic acid synthesis", Journal of Biotechnology, vol. 134, no. 1-2, pp. 146-153.
5. Nahálka, J. 2008, "Physiological aggregation of maltodextrin phosphorylase from Pyrococcus furiosus and its application in a process of batch starch degradation to alpha-D-glucose-1-phosphate.", Journal of industrial microbiology & biotechnology, vol. 35, no. 4, pp. 219-223.
6. Nahálka, J., Shao, J. & Gemeiner, P. 2007, "Oligosaccharides, neoglycoproteins and humanized plastics: Their biocatalytic synthesis and possible medical applications", Biotechnology and applied biochemistry, vol. 46, no. 1, pp. 1-12.


Figure 1.
Glycobiotechnology. Schematic view on biocatalytic synthesis of various glycostructures and their proposed medical applications. From the top: high-energy phosphate bonds are formed at high temperatures, then they are transferred to nucleotides, subsequently the nucleotides are transferred to monosaccharides and finally the monosaccharides are transferred by glycosyltransferases to specific acceptors. Antimicrobial peptides, glycosylated in this way, could be used for targeting of bacterial or viral membranes. No less interesting is preparation of defined glycostructures on surface of plastic implants.