The Department of Biomedicine

BBB seminar: Jan Holgersson

Recombinant mucin-type fusion proteins as versatile inhibitors of protein-carbohydrate interactions

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Jan Holgersson
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden

Cell surface carbohydrates are essential for a multitude of biomedically important interactions taking place at the cell surface. Carbohydrate-binding proteins are therefore significant targets for the development of carbohydrate-based inhibitors. Because of their multivalent character, monovalent low molecular-weight sugar homologues or analogues are usually poor inhibitors of these interactions. Recent advances in organic and chemoenzymatic synthesis of carbohydrates will undoubtedly increase the pace by which new multivalent carbohydrate-based drugs are developed. Knowledge gained on the glycosyltransferases involved in glycan biosynthesis can be used to engineer host cells for recombinant production of proteins with tailored glycan substitutions. In particular, recombinant mucin-type proteins can serve as natural scaffolds for the multivalent presentation of therapeutic carbohydrate determinants, and I will discuss the use of such mucin-type proteins as antibody adsorbers and inhibitors of microbial adhesion.

Selected reference:

Gustafsson, A. & Holgersson, J. A new generation of carbohydrate-based therapeutics: recombinant mucin-type fusion proteins as versatile inhibitors of protein-carbohydrate interactions. Expert Opin. Drug Discov. (2006) 1: 161-178

Host: Marion Kusche-Gullberg, Department of Biomedicine

Jan Holgersson

The research of Assoc. Prof. Jan Holgersson, head of a group at the Division of Clinical Immunology belonging to the Department of Laboratory Medicine at the Karolinska Institute in Stockholm, involves the use of recombinant mucin-type proteins with tailored carbohydrate substitutions as inhibitors of protein-carbohydrate interactions. In particular, his group is interested in assessing adjuvant effects of the recombinant mucin-type fusion proteins in triggering acquired immunity through interactions with components of the innate immune system.
Jan Holgersson is co-founder of three small biotech companies, AbSorber AB (www.absorber.se), Recopharma AB (www.recopharma.com) and NovaHep AB (www.novahep.com).

Department homepage: http://departments.ki.se/labmed/home