A new generation of carbohydrate-based therapeutics: recombinant mucin-type fusion proteins as versatile inhibitors of protein-carbohydrate interactions

被引:19
作者
Gustafsson, Anki [1 ]
Holgersson, Jan [1 ]
机构
[1] Karolinska Inst, Karolinska Univ Hosp, Div Clin Immunol, S-14186 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
carbohydrate-based inhibitor; glycoengineering; mucins; protein-carbohydrate interaction; recombinant protein;
D O I
10.1517/17460441.1.2.161
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 chemo-enzymatic 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.
引用
收藏
页码:161 / 178
页数:18
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