Patent ID: 6361777
Filing Date: 2002-03-26
Classification: A61K,C07K,Y02P

Abstract:
Method of covalently coupling a polysaccharide to a biopolymer having hydroxyl, amino and/or mercapto groups, the method comprising activating the polysaccharide with cyanogen bromide and subsequently reacting the activated polysaccharide with an aminothiol linker having the formula 1:H2Nâ€”[(CH2)m-CHR1-CR2R3-A]q-CHR4-(CHR5)p-CHR6-Sâ€”R7 whereinA is a direct bond or a group having the formula â€”{Zâ€”(CH2)m-CHR1-CHR2R3}nZâ€”, m is an integer from 0 to 5; n is an integer from 0 to 3; p is an integer from 0 to 2; q is the integer 0 or 1; R1is hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted by amino, hydroxyl, carboxyl, C1-C4 alkoxycarbonyl, carbamoyl, mono- or di-C1-C4-alkylcarbamoyl or N-(&agr;-carboxyalkyl)carbamoyl,; or, if mâ‰ 0, R1 is hydroxyl, amino or peptidyl-amino; R2 and R3 are independently hydrogen or C1-C4 alkyl, or together from an oxo group; R4 is hydrogen, C1-C4 alkyl, carboxly, C1-C4 alkoxycarbonyl, carbamoly, mono-or di-C1-C4-alkylcarbamoyl or N-(&agr;-carboxyalkyl) carbamoyl; R5 is hydrogen, methyl, hydroxy or C1-C7 acyloxy; R6 is hydrogen or methyl; R7 is hydrogen or thiol-protecting group or group having the formula â€”Sâ€”CHR6-(CHR5)p-CHR4-[Aâ€”CR2R3-CHR1-(CH2)m]q-NH2, â€ƒand Z is imino, methylimino, oxygen or sulphur; to produce a thiolated polysaccharide having the formula 2Psâ€”Oâ€”C(&boxH;NH)â€”NHâ€”[(Ch2)m-CHR1-CR2R3-A]q-CHR4-(CHR5)p-CHR6-Sâ€”R7 wherein Ps represents a polysaccharide residue and A, m, p, q, R1, R2, R3, R4, R5, R6 and R7 are as defined above, and reacting the thiolated polysaccharide with the biopolymer.