Heparin molecule containing AT binding sequence and continuous 2-O-glucuronic acid residues, preparation method and application thereof

A technology of residues and heparin, which can be applied in drug combinations, extracellular fluid diseases, blood diseases, etc., can solve the problems of poor pharmacokinetics of compounds, catalytic modification efficiency lower than that of IdoA residues, unrealistic problems, etc., to achieve good results Industrial application prospects, strong and specific anti-FXa activity, and the effect of high-quality anticoagulant and antithrombotic drugs
CN113583151AActive Publication Date: 2021-11-02SHANDONG UNIV
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
SHANDONG UNIV
Publication Date
2021-11-02

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Abstract

The invention relates to a heparin molecule containing an AT binding sequence and a continuous 2-O-glucuronic acid residue, a preparation method and application thereof. The heparin molecule comprises an AT binding sequence and a continuous 2-O-sulfated glucuronic acid (GlcA2S) residue, wherein the structural formula is shown in a formula II. According to the invention, the novel heparin molecule with the determined structure has high-effect specific anti-FXa activity, and does not have obvious anti-IIa activity, the activity of the novel heparin molecule can be reversed by protamine, and the novel heparin molecule is suitable for preparing safer and high-quality anticoagulant and antithrombotic drugs, and has a very good industrial application prospect.
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Description

technical field

[0001] The invention relates to a heparin molecule containing an AT binding sequence and a continuous 2-O-glucuronic acid residue, a preparation method and application thereof, and belongs to the technical field of biomedicine. Background technique

[0002] Heparin is an ancient natural polysaccharide anticoagulant, which belongs to the family of highly sulfated glycosaminoglycans, composed of α-L-iduronic acid (IdoA, ≥80%) or β-D-glucuronide Acid and α-D-glucosamine (GlcN) are polymerized alternately with disaccharide units linked by 1,4-glycosidic bonds, in which IdoA residues are usually 2-O-sulfated (IdoA2S, ≥85%), and GlcA rarely undergoes 2-O-sulfated GlcA (GlcA2S, <5%); more than 80% of GlcN residues are N-sulfated (GlcNS), and a small amount is N-acetylated (GlcNAc) or N-non-substituted ( GlcNH 3 + ), and 6-O-sulfation (GlcNS6S, GlcNAc6S) and / or a small amount of 3-O-sulfation (GlcNS6S3S) commonly occur, making its structure highly heterogeneous...

Claims

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