Evidence map›Paper›PMID 27611601›Full record

ArticleJournal of the American Chemical Society2016

Integrated Approach to Identify Heparan Sulfate Ligand Requirements of Robo1.

Chengli Zong, Rongrong Huang, Eduard Condac, Yulun Chiu, Wenyuan Xiao, Xiuru Li, Weigang Lu, Mayumi Ishihara, Shuo Wang, Annapoorani Ramiah and 7 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.0field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Synthesis of Sulfated Carbohydrates - Glycosaminoglycans.Handbook of experimental pharmacology · 2025
    Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Synthesis of 3-Biochemistry · 2020
    Article
  12. Article
  13. Review
  14. Glycans in drug discovery.MedChemComm · 2019
    Review
  15. Review
  16. Oligosaccharide Synthesis and Translational Innovation.Journal of the American Chemical Society · 2019
    Review
  17. Article
  18. Article
  19. Article
  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

17 authors at 4 institutions in 3 countries.

Chengli Zong
Rongrong Huang
Eduard Condac
Yulun Chiu
Wenyuan Xiao
Xiuru Li
Weigang Lu
Mayumi Ishihara
Shuo Wang
Annapoorani Ramiah
Morgan Stickney
Parastoo Azadi
I Jonathan Amster
Kelley W Moremen
Lianchun Wang
Joshua S Sharp
Geert-Jan BoonsDepartment of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Carbohydrate Competence Center · NLUniversity of Georgia · USInstitute of Bioinformatics · INUtrecht University · NL

Funding

TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
Robo4 and heparan sulfate proteoglycan in angiogenesisR01HL093339 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI WANG, LIANCHUN · 2009 to 2018
$3.4M
Using CRISPR-Cas9 technology to develop a mutant cell library for heparan sulfate structure-function studyR21HL131553 · NHLBI · UNIVERSITY OF GEORGIA · PI WANG, LIANCHUN · 2015 to 2016
$582k
NHLBI NIH HHS R01 HL093339NHLBI NIH HHS R21 HL131553NIGMS NIH HHS P41 GM103390
6 · The paper itself

Abstract

An integrated methodology is described to establish ligand requirements for heparan sulfate (HS) binding proteins based on a workflow in which HS octasaccharides are produced by partial enzymatic degradation of natural HS followed by size exclusion purification, affinity enrichment using an immobilized HS-binding protein of interest, putative structure determination of isolated compounds by a hydrophilic interaction chromatography-high-resolution mass spectrometry platform, and chemical synthesis of well-defined HS oligosaccharides for structure-activity relationship studies. The methodology was used to establish the ligand requirements of human Roundabout receptor 1 (Robo1), which is involved in a number of developmental processes. Mass spectrometric analysis of the starting octasaccharide mixture and the Robo1-bound fraction indicated that Robo1 has a preference for a specific set of structures. Further analysis was performed by sequential permethylation, desulfation, and pertrideuteroacetylation followed by online separation and structural analysis by MS/MS. Sequences of tetrasaccharides could be deduced from the data, and by combining the compositional and sequence data, a putative octasaccharide ligand could be proposed (GlA-GlcNS6S-IdoA-GlcNS-IdoA2S-GlcNS6S-IdoA-GlcNAc6S). A modular synthetic approach was employed to prepare the target compound, and binding studies by surface plasmon resonance (SPR) confirmed it to be a high affinity ligand for Robo1. Further studies with a number of tetrasaccharides confirmed that sulfate esters at C-6 are critical for binding, whereas such functionalities at C-2 substantially reduce binding. High affinity ligands were able to reverse a reduction in endothelial cell migration induced by Slit2-Robo1 signaling.

Indexed as

Cell MovementHeparan SulfateHumansLigandsNerve Tissue ProteinsProtein BindingReceptors, ImmunologicRoundabout ProteinsHeparan SulfateLigandsNerve Tissue ProteinsReceptors, ImmunologicRoundabout Proteins

Identifiers

PMID27611601
PMCPMC5068570
OpenAlexW2512055109

What OpenQuestion holds

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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.