Nanopore-regulated in situ polymerization for synthesis of homogeneous heparan sulfate with low dispersity.

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  • Additional Information
    • Source:
      Publisher: Elsevier Applied Science Publishers Country of Publication: England NLM ID: 8307156 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1344 (Electronic) Linking ISSN: 01448617 NLM ISO Abbreviation: Carbohydr Polym Subsets: MEDLINE
    • Publication Information:
      Publication: <1992-> : Barking : Elsevier Applied Science Publishers
      Original Publication: London [Eng.] : Applied Science Publishers, c1981-
    • Subject Terms:
      Heparitin Sulfate*/chemistry ; Polymerization*; Anticoagulants/chemistry ; Anticoagulants/pharmacology ; Anticoagulants/chemical synthesis ; Molecular Weight ; Porosity ; Humans ; Disaccharides/chemistry ; Glycosyltransferases/metabolism ; Glycosyltransferases/chemistry
    • Abstract:
      The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.
      Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Enzyme immobilization; Glycosylation reaction; Homogeneous heparan sulfate; Metal-organic capsule
    • Accession Number:
      9050-30-0 (Heparitin Sulfate)
      0 (heparosan)
      0 (Anticoagulants)
      0 (Disaccharides)
      EC 2.4.- (Glycosyltransferases)
    • Publication Date:
      Date Created: 20240614 Date Completed: 20240614 Latest Revision: 20240627
    • Publication Date:
      20240627
    • Accession Number:
      10.1016/j.carbpol.2024.122297
    • Accession Number:
      38876729