Asset Details
Do you wish to reserve the book?
Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control
Do you wish to request the book?
Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Paper
Enzymatic access to the rare ΔUA (1→4) Glc 3, 6, N-sulfated heparin disaccharide, implications for heparin quality control
2024
Overview
The sulfated glycosaminoglycan heparin is the most commonly used pharmaceutical anticoagulant worldwide. Heparin, which is extracted primarily from porcine sources, has a complex heterogeneous structure, resulting in a highly variable pharmaceutical product susceptible to contamination. As a by-product of the food industry, heparin is also limited by production capacity, giving rise to concerns that demand will outstrip supply. The anticoagulant activity of heparin derives principally from the AGA*IA pentasaccharide sequence, containing a rare 3-O-sulfated glucosamine, which binds and activates antithrombin. Analytical heparin digestion by the widely used Pedobacter heparinus lyases has limited activity in regions of 3-O-sulfation, rendering these enzymes poorly suited to study anticoagulant sequences. Here, we provide structural and functional characterization of a Bacteroides eggerthii lyase that exhibits highly efficient heparin depolymerization, with specificity distinct to P. heparinus. Using a panel of biophysical and structural techniques, we demonstrate that B. eggerthii lyase effectively liberates the rare GA* disaccharide, a key indicator of anticoagulant potential, from the defined heparin pentasaccharide fondaparinux. We envision superior cleavage by B. eggerthii lyases will enable the future quantitative, direct detection of anticoagulant relevant 3-O-sulfated sequences, delivering complementary structural information to existing analytical methods, with clear utility for pharmaceutical quality control workflows.
Publisher
Cold Spring Harbor Laboratory
Subject
