Methods for introducing mannose 6-phosphate and other oligosacharides onto glycoproteins
AssigneeGenzyme Corporation
InventorYunxiang ZHU
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Abstract
Methods to introduce highly phosphorylated mannopyranosyl oligosaccharide derivatives containing mannose 6-phosphate (M6P), or other oligosaccharides bearing other terminal hexoses, to carbonyl groups on oxidized glycans of glycoproteins while retaining their biological activity are described. The methods are useful for modifying glycoproteins, including those produced by recombinant protein expression systems, to increase uptake by cell surface receptor-mediated mechanisms, thus improving their therapeutic efficacy in a variety of applications.
Claims21
A method for coupling a highly phosphorylated mannopyranosyl oligosaccharide compound to a glycoprotein having at least one glycan, or to chemical compounds with a carbonyl group, said method comprising:
- derivatizing the highly phosphorylated mannopyranosyl oligosaccharide compound with a chemical compound containing a carbonyl-reactive group;
- oxidizing the glycoprotein having at least one glycan to generate at least one carbonyl (aldehyde) group on the glycoprotein;
- and
- reacting the oxidized glycoprotein having at least one glycan, or a chemical compound with a carbonyl group, with the derivatized highly phosphorylated mannopyranosyl oligosaccharide compound to form a new compound having a hydrazone bond.
Dependencies are inferred from the claim text.