Oligosaccharide-protein conjugates

摘要

Provided herein are conjugates comprising a protein and an oligosaccharide of one of Formulae I-VI. Also provided herein are pharmaceutical compositions comprising such conjugates. Further provided herein are methods of treating a lysosomal storage disorder in a mammal by administration of an oligosaccharide-glycoprotein conjugate.

主权项

1. A method of preparing a compound having the Formula VII:wherein:
R1 is chosen from hydrogen, hydroxyl, optionally substituted lower alkyl, phosphate, sulfate, —OR7, a protecting group, and a saccharide; R2, R3, R4, and R5 are each independently chosen from hydrogen, sulfate, hydroxyl, —OR8, a protecting group and a saccharide; R6 is an alkoxycarbonyl; R7 and R8 are each independently chosen from acetyl and optionally substituted lower alkyl; and n is an integer from 2 to 4; comprising:
a) treating a compound having the Formula VIII:wherein:
R1 through R5 are as defined above; and R9 and R10 are chosen from hydrogen and hydroxyl, such that when one of R9 and R10 is hydroxyl, the other is hydrogen; with a compound having the Formula R11R12(Sn═O) to form a compound having the Formula IX:wherein:
R1 through R5 are as defined above; and R11 and R12 are each independently chosen from unsubstituted alkyl, or R11 and R12, taken together, are chosen from unsubstituted alkylene; and
b) treating the compound of Formula IX, optionally in the presence of a metal fluoride, with a compound having the Formula R6—(CH2)n-L,wherein:
R6 and n are as defined above; and L is a halogen; to form the compound of Formula VII.