Evidence map›Paper›PMID 36239422›Full record

ArticleGlycobiology2023

Investigation of the pharmacokinetic properties of synthetic heparan sulfate oligosaccharides.

Katelyn Arnold, Zhangjie Wang, Andrew Lucas, William Zamboni, Yongmei Xu, Jian Liu

Open access · greenAbstract read
In one paragraph

Article in Glycobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. UtilizingAmerican journal of physiology. Cell physiology · 2025
    Review
  2. Article
  3. A 3-Frontiers in immunology · 2023
    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

6 authors at 3 institutions in 1 country.

Katelyn ArnoldDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27514, United States.
Zhangjie WangDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27514, United States.
Andrew LucasUNC Advanced Translational Pharmacology and Analytical Chemistry (ATPAC) Laboratory, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Institute of Nanomedicine, University of North Carolina, Chapel Hill, NC 27514, United States.
William ZamboniUNC Advanced Translational Pharmacology and Analytical Chemistry (ATPAC) Laboratory, UNC Eshelman School of Pharmacy, UNC Lineberger Comprehensive Cancer Center, Carolina Institute of Nanomedicine, University of North Carolina, Chapel Hill, NC 27514, United States.
Yongmei XuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27514, United States.
Jian LiuDivision of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27514, United States.
University of North Carolina at Chapel Hill · USUNC Lineberger Comprehensive Cancer CenterUniversity of North Carolina Health Care · 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
Development of heparan sulfate-based therapeutics to treat inflammatory diseasesR44GM144019 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI WANG, ZHANGJIE · 2023 to 2025
$2.4M
Development of analytical methods for glycosaminoglycans from biological sourcesR44GM142304 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI WANG, ZHANGJIE · 2022 to 2023
$2.0M
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 heparan sulfate-based therapeutics to treat inflammatory diseasesR43GM144019 · NIGMS · GLYCAN THERAPEUTICS CORPORATION · PI ARNOLD, KATELYN · 2021 to 2021
$231k
NHLBI NIH HHS R01 HL144970NIGMS NIH HHS R43 GM144019NIGMS NIH HHS R44 GM142304NIGMS NIH HHS R44 GM144019
6 · The paper itself

Abstract

Heparan sulfate (HS) is a sulfated polysaccharide with a wide range of biological activities. There is an increasing interest in the development of structurally homogeneous HS oligosaccharides as therapeutics. However, the factors influencing the pharmacokinetic properties of HS-based therapeutics remain unknown. Here, we report the pharmacokinetic properties of a panel of dodecasaccharides (12-mers) with varying sulfation patterns in healthy mice and uncover the pharmacokinetic properties of an octadecasaccharide (18-mer) in acutely injured mice. In the 12-mer panel, 1 12-mer, known as dekaparin, is anticoagulant, and 3 12-mers are nonanticoagulant. The concentrations of 12-mers in plasma and urine were determined by the disaccharide analysis using liquid chromatography coupled with tandem mass spectrometry. We observed a striking difference between anticoagulant and nonanticoagulant oligosaccharides in the 12-mer panel, showing that anticoagulant dekaparin had a 4.6-fold to 8.6-fold slower clearance and 4.4-fold to 8-fold higher plasma exposure compared to nonanticoagulant 12-mers. We also observed that the clearance of HS oligosaccharides is impacted by disease. Using an antiinflammatory 18-mer, we discovered that the clearance of 18-mer is reduced 2.8-fold in a liver failure mouse model compared to healthy mice. Our results suggest that oligosaccharides are rapidly cleared renally if they have low interaction with circulating proteins. We observed that the clearance rate of oligosaccharides is inversely associated with the degree of binding to target proteins, which can vary in response to pathophysiological conditions. Our findings uncover a contributing factor for the plasma and renal clearance of oligosaccharides which will aid the development of HS-based therapeutics.

Indexed as

AnticoagulantsHeparan SulfateAnimalsChromatography, LiquidMiceOligosaccharidesProteinsAnticoagulantsHeparan SulfateOligosaccharidesProteinsheparan sulfatepharmacokineticssynthetic oligosaccharidetherapeutics

Identifiers

PMID36239422
PMCPMC9990981
OpenAlexW4306174595

What OpenQuestion holds

Textmetadata
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.