A new generation of carbohydrate-based therapeutics: recombinant mucin-type fusion proteins as versatile inhibitors of protein–carbohydrate interactions
- 10 July 2006
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Drug Discovery
- Vol. 1 (2) , 161-178
- https://doi.org/10.1517/17460441.1.2.161
Abstract
Cell surface carbohydrates are essential for a multitude of biomedically important interactions that take place at the cell surface. Carbohydrate-binding proteins are, therefore, significant targets for the development of carbohydrate-based inhibitors. Due to 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 that are involved in glycan biosynthesis can be used to engineer host cells for recombinant production of proteins with tailored glycan substitution. In particular, recombinant mucin-type proteins can serve as natural scaffolds for multivalent presentation of therapeutic carbohydrate determinants.Keywords
This publication has 113 references indexed in Scilit:
- High‐Throughput Carbohydrate Microarray Analysis of 24 LectinsAngewandte Chemie International Edition in English, 2006
- N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venulesNature Immunology, 2005
- Tumor‐associated carbohydrate antigens: A possible avenue for cancer preventionImmunology & Cell Biology, 2005
- Carbohydrate vaccines as immunotherapy for cancerImmunology & Cell Biology, 2005
- Lymphocyte homing to the gut: attraction, adhesion, and commitmentImmunological Reviews, 2005
- Thermodynamic Binding Parameters of Individual Epitopes of Multivalent Carbohydrates to Concanavalin A As Determined by “Reverse” Isothermal Titration MicrocalorimetryBiochemistry, 2001
- Distinct Substrate Specificities of Five Human α-1,3-Fucosyltransferases forin VivoSynthesis of the Sialyl Lewis x and Lewis x EpitopesBiochemical and Biophysical Research Communications, 1997
- Structures of the O-Glycans on P-selectin Glycoprotein Ligand-1 from HL-60 CellsJournal of Biological Chemistry, 1996
- Synthesis of a Divalent Sialyl Lewis x O‐glycan, a Potent Inhibitor of Lymphocyte‐Endothelium AdhesionEuropean Journal of Biochemistry, 1995
- Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as cancer therapeutics?Immunology Today, 1993