Exploration of human xylosyltransferase for chemoenzymatic synthesis of proteoglycan linkage region
File(s)
Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
Proteoglycans (PGs) play important roles in many biological processes including tumor progression, cell adhesion, and regulation of growth factor activities. With glycosaminoglycan chains attached to the core proteins in nature, PGs are highly challenging synthetic targets due to the difficulties in integrating the sulfated glycans with the peptide backbone. To expedite the synthesis, herein, the utility of human xylosyltransferase I (XT-I), the enzyme responsible for initiating PG synthesis, has been explored. XT-I was found to be capable of efficiently installing the xylose unit onto a variety of peptide structures on mg scales. Furthermore, an unnatural sugar, i.e., 6-azidoglucose can be transferred by XT-I introducing a reactive handle onto the glycopeptide for selective functionalization. XT-I can be coupled with β-4-galactosyl transferase-7 for one pot synthesis of glycopeptides bearing galactose-xylose disaccharide, paving the way toward efficient chemoenzymatic synthesis of PG glycopeptides and glycoproteins.
Date Issued
2021-04-21
Date Acceptance
2021-03-22
Citation
Organic and Biomolecular Chemistry, 2021, 19 (15), pp.3374-3378
ISSN
1477-0520
Publisher
Royal Society of Chemistry
Start Page
3374
End Page
3378
Journal / Book Title
Organic and Biomolecular Chemistry
Volume
19
Issue
15
Copyright Statement
© The Royal Society of Chemistry 2021.
Sponsor
Wellcome Trust
Biotechnology and Biological Sciences Research Council (BBSRC)
Grant Number
101748/Z/13/Z
BB/T01279X/1
Subjects
Science & Technology
Physical Sciences
Chemistry, Organic
Chemistry
Organic Chemistry
0304 Medicinal and Biomolecular Chemistry
0305 Organic Chemistry
Publication Status
Published
Date Publish Online
2021-03-22