Highly purified fucosylated chondroitin sulfate oligomers with selective intrinsic factor Xase complex inhibition

Copyright © 2019. Published by Elsevier Ltd..

Fucosylated chondroitin sulfate (FCS) oligosaccharides of specific molecular weight have shown potent anticoagulant activities with selectivity towards intrinsic factor Xase complex. However, the preparation of FCS oligosaccharides by traditional methods requires multiple purification steps consuming large amounts of time and significant resources. The current study focuses on developing a method for the rapid preparation of FCS oligomers from sea cucumber Pearsonothuria graeffei having 6-18 saccharide residues. The key steps controlling molecular weight (Mw) and purity of these FCS oligomers were evaluated. Structural analysis showed the resulting FCS oligomers were primarily l-Fuc3,4diS-α1,3-d-GlcA-β1,3-(d-GalNAc4,6diS-β1,4-[l-Fuc3,4diS-α1,3-]d-GlcA-β1,3-)nd-anTal-ol4,6diS (n = 1˜5) accompanied by partial de-fucosylation and/or de-sulfation. In vitro and in vivo experiments demonstrate that these FCS oligomers selectively inhibit intrinsic factor Xase complex and exhibit remarkable antithrombotic activity without hemorrhagic and hypotension side effects. This method is suitable for large-scale preparation of FCS oligosaccharides as clinical anticoagulants.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:222

Enthalten in:

Carbohydrate polymers - 222(2019) vom: 15. Okt., Seite 115025

Sprache:

Englisch

Beteiligte Personen:

Yan, Lufeng [VerfasserIn]
Wang, Danli [VerfasserIn]
Zhu, Mengshan [VerfasserIn]
Yu, Yanlei [VerfasserIn]
Zhang, Fuming [VerfasserIn]
Ye, Xingqian [VerfasserIn]
Linhardt, Robert J [VerfasserIn]
Chen, Shiguo [VerfasserIn]

Links:

Volltext

Themen:

72175-66-7
9007-28-7
Anticoagulant and antithrombotic activities
Anticoagulants
Cancer procoagulant
Chondroitin Sulfates
Cysteine Endopeptidases
EC 3.4.21.22
EC 3.4.22.-
EC 3.4.22.26
Factor IXa
Factor VIIIa
Fibrinolytic Agents
Fucosylated chondroitin sulfate
Fucosylated chondroitin sulfate oligomers
Intrinsic factor Xase complex
Journal Article
Neoplasm Proteins
Partial N-deacetylation–deaminative cleavage
Ultrafiltration separation

Anmerkungen:

Date Completed 06.12.2019

Date Revised 17.12.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.carbpol.2019.115025

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM29932589X