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

Autor: Qiao M; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China., Wang Z; Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China., Zhang J; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China., Li Y; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China., Chen LA; Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of New Power Batteries, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China., Zhang F; Departments of Chemical and Biological Engineering, and Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA., Dordick JS; Departments of Chemical and Biological Engineering, and Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA., Linhardt RJ; Departments of Chemical and Biological Engineering, and Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA., Cai C; Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. Electronic address: caic@ouc.edu.cn., Huang H; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China., Zhang X; School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China. Electronic address: zhangxing@njnu.edu.cn.
Jazyk: angličtina
Zdroj: Carbohydrate polymers [Carbohydr Polym] 2024 Oct 01; Vol. 341, pp. 122297. Date of Electronic Publication: 2024 May 20.
DOI: 10.1016/j.carbpol.2024.122297
Abstrakt: 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.)
Databáze: MEDLINE
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