Title:
HEPARIN MOLECULE CONTAINING AT BINDING SEQUENCE AND CONTINUOUS 2-O-GLUCURONIC ACID RESIDUE, AND PREPARATION METHOD THEREFOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/280235
Kind Code:
A1
Abstract:
The present invention relates to a heparin molecule containing an AT binding sequence and a continuous 2-O-glucuronic acid residue, and a preparation method therefor and the use thereof. The heparin molecule contains an AT binding sequence and a continuous 2-O-sulfated glucuronic acid (GlcA2S) residue, and has a structural formula as represented by formula II. The new heparin molecule determined by the structure in the present invention has potent and specific anti-FXa activity and has no obvious anti-IIa activity, and the activity thereof can be reversed by protamine. The heparin molecule is suitable for preparing safer and high-quality anticoagulant and antithrombotic drugs, and has a very good industrial application prospects.
Inventors:
LIU CHUNHUI (CN)
MA YAQING (CN)
ZHANG GUIJIAO (CN)
MA YAQING (CN)
ZHANG GUIJIAO (CN)
Application Number:
PCT/CN2022/104216
Publication Date:
January 12, 2023
Filing Date:
July 06, 2022
Export Citation:
Assignee:
SHAN DONG UNIV (CN)
International Classes:
C08B37/10; A61P7/02; C12P19/18; C12P19/26
Foreign References:
| CN113583151A | 2021-11-02 | |||
| CN105452479A | 2016-03-30 | |||
| CN108715875A | 2018-10-30 |
Other References:
MA YAQING: "Design and Chemoenzymatic Synthesis of Novel Reversible Anticoagulant Heparin Dodecasaccharide", CHINA MASTER'S' THESES FULL-TEXT DATABASE (ELECTRONIC JOURNAL)-INFORMATION & TECHNOLOGY), TIANJIN POLYTECHNIC UNIVERSITY, CN, no. 11, 15 November 2021 (2021-11-15), CN , XP093022561, ISSN: 1674-0246
XING ZHANG, ET AL.: "Chemoenzymatic synthesis of heparan sulfate and heparin oligosaccharides and NMR analysis: paving the way to a diverse library for glycobiologists", CHEMICAL SCIENCE, ROYAL SOCIETY OF CHEMISTRY, UNITED KINGDOM, vol. 8, no. 12, 1 December 2017 (2017-12-01), United Kingdom , pages 7932 - 7940, XP055618454, ISSN: 2041-6520, DOI: 10.1039/C7SC03541A
ZHANG CHENGYING: "Uncovering the Catalytic Cleavage Mode of Heparinase Ⅰ Using Synthetic Heparin Oligosaccharides by Chemoenzymatic Method", CHINA MASTER'S' THESES FULL-TEXT DATABASE (ELECTRONIC JOURNAL)-INFORMATION & TECHNOLOGY), TIANJIN POLYTECHNIC UNIVERSITY, CN, no. 9, 15 September 2019 (2019-09-15), CN , XP093022563, ISSN: 1674-0246
NEHRU VIJI SANKARANARAYANAN; TAMARA R. STREBEL; RIO S. BOOTHELLO; KEVIN SHEERIN; ARJUN RAGHURAMAN; FLORENCE SALLAS; PHILIP D. MOSI: "A Hexasaccharide Containing Rare 2‐O‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II", ANGEWANDTE CHEMIE, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 129, no. 9, 26 January 2017 (2017-01-26), DE , pages 2352 - 2357, XP071373930, ISSN: 0044-8249, DOI: 10.1002/ange.201609541
AL NAHAIN ABDULLAH, VERA IGNJATOVIC, PAUL MONAGLE, JOHN TSANAKTSIDIS, VITO FERRO: "Heparin mimetics with anticoagulant activity", MEDICINAL RESEARCH REVIEWS, WILEY SUBSCRIPTION SERVICES, INC., A WILEY COMPANY, US, vol. 38, no. 5, 15 February 2018 (2018-02-15), US , pages 1582 - 1613, XP093022557, ISSN: 0198-6325, DOI: 10.1002/med.21489
TING WANG ET AL.: "“Chemoenzymatic synthesis of ultralow and low-molecular weight heparins”", 《BBA - PROTEINS AND PROTEOMICS》, vol. 1868, 31 October 2019 (2019-10-31), XP086038545, ISSN: 1570-9639, DOI: 10.1016/j.bbapap.2019.140301
LIU JIAN, LINHARDT ROBERT J.: "Chemoenzymatic synthesis of heparan sulfate and heparin", NATURAL PRODUCT REPORTS, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 31, no. 12, 1 January 2014 (2014-01-01), GB , pages 1676 - 1685, XP093022554, ISSN: 0265-0568, DOI: 10.1039/C4NP00076E
XING ZHANG, ET AL.: "Chemoenzymatic synthesis of heparan sulfate and heparin oligosaccharides and NMR analysis: paving the way to a diverse library for glycobiologists", CHEMICAL SCIENCE, ROYAL SOCIETY OF CHEMISTRY, UNITED KINGDOM, vol. 8, no. 12, 1 December 2017 (2017-12-01), United Kingdom , pages 7932 - 7940, XP055618454, ISSN: 2041-6520, DOI: 10.1039/C7SC03541A
ZHANG CHENGYING: "Uncovering the Catalytic Cleavage Mode of Heparinase Ⅰ Using Synthetic Heparin Oligosaccharides by Chemoenzymatic Method", CHINA MASTER'S' THESES FULL-TEXT DATABASE (ELECTRONIC JOURNAL)-INFORMATION & TECHNOLOGY), TIANJIN POLYTECHNIC UNIVERSITY, CN, no. 9, 15 September 2019 (2019-09-15), CN , XP093022563, ISSN: 1674-0246
NEHRU VIJI SANKARANARAYANAN; TAMARA R. STREBEL; RIO S. BOOTHELLO; KEVIN SHEERIN; ARJUN RAGHURAMAN; FLORENCE SALLAS; PHILIP D. MOSI: "A Hexasaccharide Containing Rare 2‐O‐Sulfate‐Glucuronic Acid Residues Selectively Activates Heparin Cofactor II", ANGEWANDTE CHEMIE, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 129, no. 9, 26 January 2017 (2017-01-26), DE , pages 2352 - 2357, XP071373930, ISSN: 0044-8249, DOI: 10.1002/ange.201609541
AL NAHAIN ABDULLAH, VERA IGNJATOVIC, PAUL MONAGLE, JOHN TSANAKTSIDIS, VITO FERRO: "Heparin mimetics with anticoagulant activity", MEDICINAL RESEARCH REVIEWS, WILEY SUBSCRIPTION SERVICES, INC., A WILEY COMPANY, US, vol. 38, no. 5, 15 February 2018 (2018-02-15), US , pages 1582 - 1613, XP093022557, ISSN: 0198-6325, DOI: 10.1002/med.21489
TING WANG ET AL.: "“Chemoenzymatic synthesis of ultralow and low-molecular weight heparins”", 《BBA - PROTEINS AND PROTEOMICS》, vol. 1868, 31 October 2019 (2019-10-31), XP086038545, ISSN: 1570-9639, DOI: 10.1016/j.bbapap.2019.140301
LIU JIAN, LINHARDT ROBERT J.: "Chemoenzymatic synthesis of heparan sulfate and heparin", NATURAL PRODUCT REPORTS, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 31, no. 12, 1 January 2014 (2014-01-01), GB , pages 1676 - 1685, XP093022554, ISSN: 0265-0568, DOI: 10.1039/C4NP00076E
Attorney, Agent or Firm:
JINAN JINDI INTELLECTUAL PROPERTY AGENCY CO., LTD (CN)
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