Sugar chain-attached linker, compound containing sugar chain-attached linker and physiologically active substance or salt thereof, and method for producing same

A method for producing a compound comprising a glycosylated linker moiety and a physiologically active substance moiety, or a salt thereof, wherein the glycosylated linker is represented by the following formula (A):

• X—R1—Y—R2 (A)
• wherein
• X represents an oxygen atom (O) having a leaving group or a sulfur atom (S) having a leaving group;
• R1 is substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, substituted or unsubstituted C2-C5 alkenyl, or substituted or unsubstituted C2-C5 alkynyl, or R1 represents —R3—R4—, —R4—R5—, or —R3—R4-R5—, wherein R3 and R5 each represent substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C2-C5 alkenyl, or substituted or unsubstituted C2-C5 alkynyl, and R4 represents substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, or a sulfur atom (S);
• Y may be present or absent, and when Y is present, Y represents —CO— or —CONH, with the proviso that C is bonded to R1 and N is bonded to R2;
• and
• R2 is a sugar chain, a glycosylated amino acid, or a glycosylated polypeptide, or R2 represents —R6—R7, wherein R6 represents a sugar chain, a glycosylated amino acid, or a glycosylated polypeptide, and R7 represents a hydrogen atom (H), substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, a nucleic acid, or PEG, and
• the physiologically active substance has at least one carboxy group,
• the method comprising the following step:
• (a) carrying out condensation reaction so as to form an ester bond or a thioester bond between the oxygen atom (O) or the sulfur atom (S) having a leaving group in the glycosylated linker and the carboxy group of the physiologically active substance.

A method for producing a compound comprising a glycosylated linker moiety and a physiologically active substance moiety, or a salt thereof, wherein the physiologically active substance has at least one carboxy group, the method comprising the following steps:

• (a) bonding a linker represented by the following formula (B) to a resin, the linker being represented by the following formula (B):
• X—R1—Y—R2 (B)
• wherein
• X represents an oxygen atom (O) having a leaving group or a sulfur atom (S) having a leaving group;
• R1 is substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, substituted or unsubstituted C2-C5 alkenyl, or substituted or unsubstituted C2-C5 alkynyl, or R1 represents —R3—R4—, —R4—R5—, or —R3—R4-R5—, wherein R3 and R5 each represent substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C2-C5 alkenyl, or substituted or unsubstituted C1-C5 alkynyl, and R4 represents substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, or a sulfur atom (S);
• Y may be present or absent, and when Y is present, Y represents —CO— or —CONH, with the proviso that C is bonded to R1 and N is bonded to R2);
• and
• R2 is an amino acid or a polypeptide, or R2 represents —R6—R7, wherein R6 represents an amino acid or a polypeptide, and R7 represents a hydrogen atom (H), —NH2, substituted or unsubstituted C1-C5 alkyl, substituted or unsubstituted C5-C16 aryl, substituted or unsubstituted C5-C16 heteroaryl, a nucleic acid, or PEG, wherein in this step, the carboxy group of the amino acid or the polypeptide represented by R2 in the linker binds to the resin;
• (b) bonding the linker bonded to the resin to the physiologically active substance, wherein the linker binds to the physiologically active substance through an ester bond or a thioester bond formed with the carboxy group of the physiologically active substance by the elimination of the leaving group in the oxygen atom (O) or the sulfur atom (S);
• and
• (c) adding a sugar chain to a side chain of the amino acid or the polypeptide represented by R2 in the linker.