Evidence map›Paper›PMID 33026409›Full record

ArticleOrganic & biomolecular chemistry2020

Using engineered 6-

Lin Yi, Yongmei Xu, Andrea M Kaminski, Xiaobing Chang, Vijayakanth Pagadala, Maurice Horton, Guowei Su, Zhangjie Wang, Genmin Lu, Pamela Conley and 3 more

Open access · greenAbstract read
In one paragraph

Article in Organic & biomolecular chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

8 citing papers in PubMed, 13 citations in OpenAlex.

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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

13 authors at 5 institutions in 2 countries.

Lin YiDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Yongmei XuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu.
Andrea M KaminskiGenome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, USA. pederse2@niehs.nih.gov.
Xiaobing ChangJiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Vijayakanth PagadalaGlycan Therapeutics, LLC, Raleigh, North Carolina, USA.ORCID 0000-0001-7349-4230
Maurice HortonDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu.
Guowei SuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu and Glycan Therapeutics, LLC, Raleigh, North Carolina, USA.
Zhangjie WangDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu.
Genmin LuBiology Department, Portola Pharmaceuticals, Inc., South San Francisco, California, USA.
Pamela ConleyBiology Department, Portola Pharmaceuticals, Inc., South San Francisco, California, USA.
Zhenqing ZhangJiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.ORCID 0000-0003-2490-5026
Lars C PedersenGenome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, USA. pederse2@niehs.nih.gov.ORCID 0000-0002-4488-4077
Jian LiuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Jian_liu@unc.edu.ORCID 0000-0001-8552-1400
University of North Carolina at Chapel Hill · USChina Pharmaceutical University · CNNational Institutes of Health · USPortola Pharmaceuticals (United States) · USGlycoMira Therapeutics (United States) · US

Funding

Crystallographic studies of macromolecular structuresZIAES102645 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI PEDERSEN, LARS · 2009 to 2017
$9.4M
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
Development of dekaparin to replace animal-sourced heparinR44HL139187 · NHLBI · GLYCAN THERAPEUTICS CORPORATION · PI PAGADALA, VIJAYAKANTH · 2019 to 2025
$4.2M
Diverse Heparan Sulfate Oligosaccharide Libraries For Understanding and Therapeutically Manipulating GlycosaminoglycansR44GM134738 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI PAGADALA, VIJAYAKANTH · 2019 to 2021
$3.2M
Reactor for Insect Cell CultureR42GM128484 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI XU, YONGMEI · 2018 to 2020
$1.9M
Synthesis and Pharmacological Evaluation of Homogenous Ultra-Low Molecular Weight HeparinsR01HL144970 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIAN · 2019 to 2021
$946k
Development of a New Carbohydrate-based Anticoagulant DrugR41HL139187 · NHLBI · GLYCAN THERAPEUTICS CORPORATION · PI LIU, JIAN · 2017 to 2017
$225k
Intramural NIH HHS ZIA ES102645NHLBI NIH HHS R01 HL094463NHLBI NIH HHS R01 HL144970NHLBI NIH HHS R41 HL139187NHLBI NIH HHS R44 HL139187NIGMS NIH HHS R42 GM128484NIGMS NIH HHS R44 GM134738
6 · The paper itself

Abstract

Heparan sulfate (HS) and heparin are sulfated polysaccharides exhibiting diverse physiological functions. HS 6-O-sulfotransferase (6-OST) is a HS biosynthetic enzyme that transfers a sulfo group to the 6-OH position of glucosamine to synthesize HS with desired biological activities. Chemoenzymatic synthesis is a widely adopted method to obtain HS oligosaccharides to support biological studies. However, this method is unable to synthesize all possible structures due to the specificity of natural enzymes. Here, we report the use of an engineered 6-OST to achieve fine control of the 6-O-sulfation. Unlike wild type enzyme, the engineered 6-OST only sulfates the non-reducing end glucosamine residue. Utilizing the engineered enzyme and wild type enzyme, we successfully completed the synthesis of five hexasaccharides and one octasaccharide differing in 6-O-sulfation patterns. We also identified a hexasaccharide construct as a new anticoagulant drug candidate. Our results demonstrate the feasibility of using an engineered HS biosynthetic enzyme to prepare HS-based therapeutics.

Indexed as

AnticoagulantsHeparinProtein EngineeringSulfotransferasesHumansAnticoagulantsHeparinheparitin sulfotransferaseSulfotransferases

Identifiers

PMID33026409
PMCPMC7646985
OpenAlexW3089437932

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.