Jump to main content
Jump to site search

Issue 40, 2020
Previous Article Next Article

Using engineered 6-O-sulfotransferase to improve the synthesis of anticoagulant heparin

Author affiliations

Abstract

Heparan sulfate (HS) and heparin are sulfated polysaccharides exhibiting diverse physiological functions. HS 6-O-sulfotransferase (6-OST) is a HS biosynthetic enzyme that transfers a sulfo group to the 6-OH position of glucosamine to synthesize HS with desired biological activities. Chemoenzymatic synthesis is a widely adopted method to obtain HS oligosaccharides to support biological studies. However, this method is unable to synthesize all possible structures due to the specificity of natural enzymes. Here, we report the use of an engineered 6-OST to achieve fine control of the 6-O-sulfation. Unlike wild type enzyme, the engineered 6-OST only sulfates the non-reducing end glucosamine residue. Utilizing the engineered enzyme and wild type enzyme, we successfully completed the synthesis of five hexasaccharides and one octasaccharide differing in 6-O-sulfation patterns. We also identified a hexasaccharide construct as a new anticoagulant drug candidate. Our results demonstrate the feasibility of using an engineered HS biosynthetic enzyme to prepare HS-based therapeutics.

Graphical abstract: Using engineered 6-O-sulfotransferase to improve the synthesis of anticoagulant heparin

Back to tab navigation

Supplementary files

Article information


Submitted
22 Aug 2020
Accepted
27 Sep 2020
First published
29 Sep 2020

Org. Biomol. Chem., 2020,18, 8094-8102
Article type
Paper

Using engineered 6-O-sulfotransferase to improve the synthesis of anticoagulant heparin

L. Yi, Y. Xu, A. M. Kaminski, X. Chang, V. Pagadala, M. Horton, G. Su, Z. Wang, G. Lu, P. Conley, Z. Zhang, L. C. Pedersen and J. Liu, Org. Biomol. Chem., 2020, 18, 8094
DOI: 10.1039/D0OB01736A

Social activity

Search articles by author

Spotlight

Advertisements