Literature DB >> 27445159

Bioengineered human heparin with anticoagulant activity.

Megan S Lord1, Bill Cheng2, Fengying Tang2, J Guy Lyons3, Jelena Rnjak-Kovacina2, John M Whitelock2.   

Abstract

Heparin is a carbohydrate anticoagulant used clinically to prevent thrombosis, however impurities can limit its efficacy. Here we report the biosynthesis of heparin-like heparan sulfate via the recombinant expression of human serglycin in human cells. The expressed serglycin was also decorated with chondroitin/dermatan sulfate chains and the relative abundance of these glycosaminoglycan chains changed under different concentrations of glucose in the culture medium. The recombinantly expressed serglycin produced with 25mM glucose present in the culture medium was found to possess anticoagulant activity one-seventh of that of porcine unfractionated heparin, demonstrating that bioengineered human heparin-like heparan sulfate may be a safe next-generation pharmaceutical heparin. Crown
Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Glycosaminoglycan; Heparin; Proteoglycan; Recombinant expression; Serglycin

Mesh:

Substances:

Year:  2016        PMID: 27445159     DOI: 10.1016/j.ymben.2016.07.006

Source DB:  PubMed          Journal:  Metab Eng        ISSN: 1096-7176            Impact factor:   9.783


  6 in total

1.  Hyaluronidase-4 is produced by mast cells and can cleave serglycin chondroitin sulfate chains into lower molecular weight forms.

Authors:  Brooke L Farrugia; Shuji Mizumoto; Megan S Lord; Robert L O'Grady; Rhiannon P Kuchel; Shuhei Yamada; John M Whitelock
Journal:  J Biol Chem       Date:  2019-06-07       Impact factor: 5.157

2.  Platelet Factor 4 Binds to Vascular Proteoglycans and Controls Both Growth Factor Activities and Platelet Activation.

Authors:  Megan S Lord; Bill Cheng; Brooke L Farrugia; Simon McCarthy; John M Whitelock
Journal:  J Biol Chem       Date:  2017-01-23       Impact factor: 5.157

3.  Optimization of bioengineered heparin/heparan sulfate production for therapeutic applications.

Authors:  Megan S Lord; MoonSun Jung; John M Whitelock
Journal:  Bioengineered       Date:  2017-04-10       Impact factor: 3.269

4.  Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors.

Authors:  Ha Na Kim; John M Whitelock; Megan S Lord
Journal:  Molecules       Date:  2017-05-15       Impact factor: 4.411

5.  Macrophages bind LDL using heparan sulfate and the perlecan protein core.

Authors:  Chun-Yi Ng; John M Whitelock; Helen Williams; Ha Na Kim; Heather J Medbury; Megan S Lord
Journal:  J Biol Chem       Date:  2021-03-05       Impact factor: 5.157

6.  Dissecting structure-function of 3-O-sulfated heparin and engineered heparan sulfates.

Authors:  Richard Karlsson; Pradeep Chopra; Apoorva Joshi; Zhang Yang; Sergey Y Vakhrushev; Thomas Mandel Clausen; Chelsea D Painter; Gergo P Szekeres; Yen-Hsi Chen; Daniel R Sandoval; Lars Hansen; Jeffrey D Esko; Kevin Pagel; Douglas P Dyer; Jeremy E Turnbull; Henrik Clausen; Geert-Jan Boons; Rebecca L Miller
Journal:  Sci Adv       Date:  2021-12-22       Impact factor: 14.136

  6 in total

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