NOVEL SYNTHETIC N-LINKED SIALO-GLYCAN-CONTAINING POLYMER AND METHOD FOR PRODUCING THE SAME

• US 20100168366A1
• Filed: 06/24/2008
• Published: 07/01/2010
• Est. Priority Date: 06/28/2007
• Status: Active Grant

• Current Assignee: National University Corporation Shizuoka University, Shizuoka Prefectural Universities Corporation, Yamasa Corporation
• Original Assignee: National University Corporation Shizuoka University, Shizuoka Prefectural Universities Corporation, Yamasa Corporation
• Inventors: Ohba, Yusuke, Hamamoto, Tomoki, Usui, Taiichi, Murata, Takeomi, Jwa, Ilpal, Suzuki, Takashi, Noguchi, Toshitada
• Granted Patent: US 8,450,441 B2
• Time in Patent Office: Days
• US Class Current: 527/312
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C08G 69/04 Preparatory processes
• CPC Class Codes: C08G 69/10 Alpha-amino-carboxylic acids polysuccinimides C08G73/1092
• CPC Class Codes: C08G 69/40 Polyamides containing oxygen in the form of ether groups C08G69/12, C08G69/32 take precedence
• CPC Class Codes: C08G 69/48 Polymers modified by chemical after-treatment

Abstract

A polymer containing an N-linked sialo-glycan wherein a sialo-glycan is condensed to a γ-polyglutamic acid using a chemical compound having an amino group on one end and a carboxyl group on another end and represented by the structural formula (I). Formula (I) (In the formula, Z means a hydroxy group or a residue represented by the formula (II), and n represents an integer of 10 or more, with the proviso that any one or more of the Z'"'"'s is represented by the formula in (II).) Formula (II) (In the formula, X means a hydroxy group or an acetylamino group, Y₁ and Y₂ mean a hydroxyl group or an N-acetylneuraminic acid residue, L means a hydrocarbon, an m represents 0 or an integer of 1 or 2, with the proviso that Y₁ and Y₂ are not the same.)

Claims

1. An N-linked sialo-glycan-containing polymer wherein a sialo-glycan is condensed to a γ

-polyglutamic acid using a chemical compound having an amino group on one end and a carboxyl group on another end as a linker and represented by the structural formula (I) below.

(In the formula (I), Z means a hydroxy group or a residue represented by the formula (II), and n represents an integer of 10 or more, with the proviso that any one or more of the Z'"'"'s is represented by the formula in (II).)

(In the formula (II), X means a hydroxy group or an acetylamino group, Y₁ and Y₂ mean a hydroxyl group or an N-acetylneuraminic acid residue, L means a hydrocarbon, an m represents 0 or an integer of 1 or 2, with the proviso that Y₁ and Y₂ are not the same.)

2. The N-linked sialo-glycan-containing polymer according to claim 1, wherein the linker is an ω

-amino acid.

3. The N-linked sialo-glycan-containing polymer according to claim 1, wherein the hydrocarbon represented by L is a hydrocarbon with a carbon number of 1-30.

4. The N-linked sialo-glycan-containing polymer according to claim 1, wherein the hydrocarbon represented by L is an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, an aralkyl group, a cycloalkyl substituted alkyl group or a hydrocarbon condensed with an amide bond of two or more of these.

5. A production method of an N-linked sialo-glycan-containing polymer comprising:

forming amide bond as a linker, a chemical compound having an amino group and a carboxyl group on each end of the compound respectively, with a 1-amino sugar in which a 1 position of a reducing terminal of the sugar is aminated and obtaining an N-linked asialo-glycan having an asialo-glycan part on a non-reducing terminal of a sugar;

synthesizing an asialo-glycan-containing polymer by condensing the N-linked asialo-glycan to a carboxyl group of a polyglutamic acid via an amino group of the linker which is linked to a reducing terminal of the N-linked asialo-glycan; and

obtaining the N-linked sialo-glycan-containing polymer by sialylation of the asialo-glycan-containing polymer.

6. The production method of an N-linked sialo-glycan-containing polymer according to claim 5, wherein the linker is an ω

-amino acid.

7. The production method of an N-linked sialo-glycan-containing polymer according to claim 5, wherein a hydrocarbon represented by L is a hydrocarbon with a carbon number of 1-30.

8. The production method of an N-linked sialo-glycan-containing polymer according to claim 5, wherein a hydrocarbon represented by L is an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, an aralkyl group, a cycloalkyl substituted alkyl group or a hydrocarbon condensed with an amide bond of two or more of these.

9. A production method of an N-linked sialo-glycan-containing polymer comprising:

forming amide bond as a linker, a chemical compound having an amino group and a carboxyl group on each end of the compound respectively, with a 1-amino sugar in which a 1 position of a reducing terminal of the sugar is aminated and obtaining an N-linked asialo-glycan having an asialo-glycan part on a non-reducing terminal of a sugar;

obtaining the N-linked sialo-glycan in which a sialo-glycan is synthesized to the non-reducing terminal side by sialylation of the N-linked asialo-glycan; and

synthesizing an sialo-glycan-containing polymer by condensing the N-linked sialo-glycan to a carboxyl group of a polyglutamic acid via an amino group of the linker which is linked to a reducing terminal of the N-linked sialo-glycan.

10. The production method of an N-linked sialo-glycan-containing polymer according to claim 9, wherein γ

-polyglutamic acid is dissolved in a mixed solution including water or a buffer and an organic solvent, and the N-linked sialo-glycan is condensed with the γ

-polyglutamic acid after activating the γ

-polyglutamic acid using an active esterification agent of a carboxyl group, and condensing agent and/or additive.

11. The production method of an N-linked sialo-glycan-containing polymer according to claim 9, wherein the linker is an ω

-amino acid.

12. The production method of an N-linked sialo-glycan-containing polymer according to claim 9, wherein a hydrocarbon represented by L is a hydrocarbon with a carbon number of 1-30.

13. The production method of an N-linked sialo-glycan-containing polymer according to claim 9, wherein a hydrocarbon represented by L is an alkyl group, an alkenyl group, a cycloalkyl group, an aryl group, an aralkyl group, a cycloalkyl substituted alkyl group or an amide linked hydrocarbon of two or more of these.