Evidence map›Paper›PMID 25817684›Full record

ArticleCarbohydrate polymers2015

Combinatorial one-pot chemoenzymatic synthesis of heparin.

Ujjwal Bhaskar, Guoyun Li, Li Fu, Akihiro Onishi, Mathew Suflita, Jonathan S Dordick, Robert J Linhardt

Abstract read
In one paragraph

Article in Carbohydrate polymers, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 66 citations in OpenAlex.

  1. Synthetic biology for heparin biomanufacturing.Bioresources and bioprocessing · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Heterologous production of chondroitin.Biotechnology reports (Amsterdam, Netherlands) · 2022
    Review
  7. Review
  8. Article
  9. Bioengineered production of glycosaminoglycans and their analogues.Systems microbiology and biomanufacturing · 2021
    Article
  10. Enzymatic Synthesis of Glycans and Glycoconjugates.Advances in biochemical engineering/biotechnology · 2021
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Engineered heparins as new anticoagulant drugs.Bioengineering & translational medicine · 2017
    Review
  19. Heparin: Past, Present, and Future.Pharmaceuticals (Basel, Switzerland) · 2016
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Ujjwal BhaskarDepartment of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Guoyun LiDepartment of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Li FuDepartment of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Akihiro OnishiDepartment of Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Mathew SuflitaDepartment of Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Jonathan S DordickDepartment of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA.
Robert J LinhardtDepartment of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biology, Rensselaer Polytechnic Institute, Troy, NY, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA; Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, USA. Electronic address: linhar@rpi.edu.
Rensselaer Polytechnic Institute · US

Funding

In vitro synthesis of recombinant heparan sulfateR01HL094463 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN, PAWLINSKI, RAFAL L · 2009 to 2021
$5.2M
Synthetic Heparan Sulfate: Probing Biosynthesis to Prepare Defined DrugsR01HL062244 · NHLBI · UNIVERSITY OF IOWA · PI DEANGELIS, PAUL L, LINHARDT, ROBERT J · 2001 to 2016
$4.1M
Development of a Bioengineered Heparin from a Non-Animal SourceR01HL096972 · NHLBI · RENSSELAER POLYTECHNIC INSTITUTE · PI DORDICK, JONATHAN S., LINHARDT, ROBERT J · 2009 to 2013
$3.9M
SEQUENCING THE POLYSACCHARIDE COMPONENT OF PROTEOGLYCANSR01GM038060 · NIGMS · UNIVERSITY OF IOWA · PI LINHARDT, ROBERT J · 1988 to 2012
$2.8M
NHLBI NIH HHS HL094463NHLBI NIH HHS HL096972NHLBI NIH HHS HL62244NHLBI NIH HHS R01 HL062244NHLBI NIH HHS R01 HL094463NHLBI NIH HHS R01 HL096972NIGMS NIH HHS GM38060NIGMS NIH HHS R01 GM038060
6 · The paper itself

Abstract

Contamination in heparin batches during early 2008 has resulted in a significant effort to develop a safer bioengineered heparin using bacterial capsular polysaccharide heparosan and recombinant enzymes derived from the heparin/heparan sulfate biosynthetic pathway. This requires controlled chemical N-deacetylation/N-sulfonation of heparosan followed by epimerization of most of its glucuronic acid residues to iduronic acid and O-sulfation of the C2 position of iduronic acid and the C3 and C6 positions of the glucosamine residues. A combinatorial study of multi-enzyme, one-pot, in vitro biocatalytic synthesis, carried out in tandem with sensitive analytical techniques, reveals controlled structural changes leading to heparin products similar to animal-derived heparin active pharmaceutical ingredients. Liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analysis confirms an abundance of heparin's characteristic trisulfated disaccharide, as well as 3-O-sulfo containing residues critical for heparin binding to antithrombin III and its anticoagulant activity. The bioengineered heparins prepared using this simplified one-pot chemoenzymatic synthesis also show in vitro anticoagulant activity.

Indexed as

AnimalsAnticoagulantsBioengineeringChromatography, High Pressure LiquidChromatography, LiquidFactor XaHeparinMagnetic Resonance SpectroscopyMass SpectrometryProthrombinSulfotransferasesAnticoagulantsFactor IIaFactor XaHeparinProthrombinSulfotransferasesBioengineered heparinLiquid chromatography–mass spectrometryNuclear magnetic resonance spectroscopyOne-pot synthesisUnited States Pharmacopeia

Identifiers

PMID25817684
PMCPMC4379424
OpenAlexW2131388671

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.