Biotinylated hexadecasaccharides, preparation and use thereof
View Patent ↗The invention concerns novel biotinylated hexadecasaccharides of general formula (I) wherein: Biot is a biotin derivative; R, R 1 and R 2 , represent independently of one another a C 1 -C 6 alkoxy or and —OSO 3 ; R 3 represents a C 1 -C 6 alkoxy or an —OSO 3 , or R 3 constitutes a —O—CH 2 — bridge; Pe represents a saccharide concatenation; as well as their pharmaceutically acceptable salts, and their use as medicines.
1. A biotinylated hexadecasaccharide of general formula I:
in which:
T represents a sequence T 1 or T 2 having the following formulae:
Biot represents the group:
R represents a (C 1 -C 6 )alkoxy radical, or an —OSO 3 − radical;
R 1 represents a (C 1 -C 6 )alkoxy radical, or an —OSO 3 − radical;
R 2 represents a (C 1 -C 6 )alkoxy radical or an —OSO 3 − radical;
R 3 represents a (C 1 -C 6 )alkoxy radical, or an —OSO 3 − radical, or alternatively R 3 constitutes an —O—CH 2 — bridge, the —CH 2 — group being linked to the carbon atom bearing the carboxylic function on the same ring; and
Pe represents a saccharide sequence having the following formula:
and a pharmaceutically acceptable salt thereof.
2. The biotinylated hexadecasaccharide according to claim 1 of general formula I, in which —R represents a methoxy radical or an —OSO 3 − radical,
R 1 represents a methoxy radical,
R 2 represents an —OSO 3 − radical, and
R 3 represents a methoxy radical.
3. The biotinylated hexadecasaccharide according to claim 1 , chosen from:
methyl (2,3,4,6-tetra-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-β-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)-[(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1→4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)] 3 -(2-[N-(6-biotinamido hexanoyl)]-2-deoxy-3-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-α-L-idopyranosyl-uronic acid)-(1→4)-3-O-methyl-2,6-di-O-sulfonato-α-D-glucopyranoside, sodium salt; and
methyl (2,3,4,6-tetra-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-β-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)-[(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1→4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)] 3 -(2-[N-(6-biotinamido hexanoyl)]-2-deoxy-3-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-α-L-idopyranosyl-uronic acid)-(1→4)-2,3,6-tri-O-sulfonato-α-D-glucopyranoside, sodium salt.
4. The biotinylated hexadecasaccharide according to claim 3 , wherein the biotinylated hexadecasaccharide is methyl (2,3,4,6-tetra-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-β-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)-[(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1→4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)] 3 -(2-[N-(6-biotinamido hexanoyl)]-2-deoxy-3-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-α-L-idopyranosyl-uronic acid)-(1→4)-3-O-methyl-2,6-di-O-sulfonato-α-D-glucopyranoside, sodium salt.
5. The biotinylated hexadecasaccharide according to claim 3 , wherein the biotinylated hexadecasaccharide is methyl (2,3,4,6-tetra-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-sulfonato-β-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)-[(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1→4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1→4)] 3 -(2-[N-(6-biotinamido hexanoyl)]-2-deoxy-3-O-methyl-6-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1→4)-(2,3,6-tri-O-sulfonato-α-D-glucopyranosyl)-(1→4)-(2,3-di-O-methyl-α-L-idopyranosyl-uronic acid)-(1→4)-2,3,6-tri-O-sulfonato-α-D-glucopyranoside, sodium salt.
6. A pharmaceutical composition containing, as active principle, a biotinylated hexadecasaccharide according to claim 1 , in combination with at least one inert and suitable excipient.
7. A method of neutralizing a biotinylated hexadecasaccharide according to claim 1 , comprising: contacting said biotinylated hexadecasaccharide with avidin.
8. A method of neutralizing a biotinylated hexadecasaccharide according to claim 1 , comprising: contacting said biotinylated hexadecasaccharide with streptavidin.