Differential Carbohydrate Recognition of Two GlcNAc-6-sulfotransferases with Possible Roles in L-Selectin Ligand Biosynthesis

Two human GlcNAc-6-sulfotransferases, CHST2 and HEC-GlcNAc6ST, have been recently identified as possible contributors to the inflammatory response by virtue of their participation in L-selectin ligand biosynthesis. Selective inhibitors would facilitate their functional elucidation and might provide...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Chemical Society 2000-09, Vol.122 (36), p.8612-8622
Main Authors: Cook, Brian N, Bhakta, Sunil, Biegel, Teresa, Bowman, Kendra G, Armstrong, Joshua I, Hemmerich, Stefan, Bertozzi, Carolyn R
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two human GlcNAc-6-sulfotransferases, CHST2 and HEC-GlcNAc6ST, have been recently identified as possible contributors to the inflammatory response by virtue of their participation in L-selectin ligand biosynthesis. Selective inhibitors would facilitate their functional elucidation and might provide leads for antiinflammatory therapy. Here we investigate the critical elements of a disaccharide substrate that are required for recognition by CHST2 and HEC-GlcNAc6ST. A panel of disaccharide analogues, bearing modifications to the pyranose rings and aglycon substituents, were synthesized and screened for substrate activity with each enzyme. Both GlcNAc-6-sulfotransferases required the 2-N-acetamido and 4-hydroxyl groups of a terminal GlcNAc residue for conversion to product. Both enzymes tolerated modifications to the reducing terminal pyranose. Key differences in recognition of an amide group in the aglycon substituent were observed, providing the basis for future glycomimetic inhibitor design.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja001224k