Sialic acid derivatives
An amine or hydrazide derivative of a sialic acid unit, e.g. in a polysaccharide, is reacted with a bifunctional reagent at least one of the functionalities of which is an ester of N-hydroxy succinimide, to form an amide or hydrazide product. The product has a useful functionality, which allows it to be conjugated, for instance to proteins, drugs, drug delivery systems or the like. The process is of particular utility for derivatising amine groups introduced in sialic acid terminal groups of polysialic acids.
1. A compound of formula III or formula VIII
wherein X is a functional group selected from the group consisting of NHS-esters, vinyl sulfone, N-maleimido, N-iodoacetamido, orthopyridyl disulfide, hydroxy, protected hydroxyl, amino, protected amino, carboxyl, protected carboxyl, and azido groups;
R 1 is a linker;
R 4 is hydrogen or C 1-4 alkyl; and
R 3 is a mono-, di-, oligo- or poly-saccharide, a protein, a peptide, a lipid, a drug or a drug delivery system.
2. A compound according to claim 1 wherein R 1 is selected from the group consisting of alkanediyl, arylene, alkarylene, heteroarylene and alkylheteroarylene, any of which is optionally interrupted by carbonyl, ester, sulfide, ether, amide and/or amine linkages.
3. A compound according to claim 1 wherein R 1 is C 3 -C 6 alkanediyl.
4. A compound according to claim 1 wherein R 3 is an oligo or poly-saccharide.
5. A compound according to claim 4 wherein R 3 is oligo- or poly-sialic acid.