Evidence map›Paper›PMID 25824568›Full record

ArticleNature communications2015

Glycopeptide analogues of PSGL-1 inhibit P-selectin in vitro and in vivo.

Venkata R Krishnamurthy, Mohammed Y R Sardar, Yu Ying, Xuezheng Song, Carolyn Haller, Erbin Dai, Xiaocong Wang, Donny Hanjaya-Putra, Lijun Sun, Vasilios Morikis and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 92 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Computational Pipeline for Accelerating the Design of Glycomimetics.Journal of chemical information and modeling · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Silver Oxide Promoted Synthesis of AlphaThe Journal of organic chemistry · 2025
    Article
  9. Article
  10. Review
  11. Review
  12. The roles of P-selectin in cancer cachexia.Medical oncology (Northwood, London, England) · 2023
    Review
  13. Article
  14. Article
  15. TargetingPulmonary circulation · 2023
    Article
  16. Effector Memory-Expressing CD45RA (TEMRA) CD8Journal of the American Society of Nephrology : JASN · 2022
    Article
  17. Computationally guided conversion of the specificity of E-selectin to mimic that of Siglec-8.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  18. Review
  19. Article
  20. Review
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

14 authors at 5 institutions in 1 country.

Venkata R Krishnamurthy1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Mohammed Y R Sardar1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Yu YingDepartment of Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
Xuezheng SongDepartment of Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
Carolyn Haller1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Erbin Dai1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Xiaocong WangComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA.
Donny Hanjaya-Putra1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Lijun SunDepartment of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA.
Vasilios MorikisDepartment of Biomedical Engineering, University of California Davis, Davis, California 95616, USA.
Scott I SimonDepartment of Biomedical Engineering, University of California Davis, Davis, California 95616, USA.
Robert J Woods1] Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA [2] School of Chemistry, National University of Ireland, Galway, University Road, Galway, Ireland.
Richard D CummingsDepartment of Biochemistry, Emory University, Atlanta, Georgia 30322, USA.
Elliot L Chaikof1] Department of Surgery, Center for Drug Discovery and Translational Research, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Suite 9F, Boston, Massachusetts 02215, USA [2] Wyss Institute of Biologically Inspired Engineering, Harvard University, 110 Francis Street, Suite 9F, Boston, Massachusetts 02115, USA.
Harvard University · USEmory University · USUniversity of California, Davis · USUniversity of Georgia · USBeth Israel Deaconess Medical Center · US

Funding

Protein-glycan Interactions in the Vascular SystemP01HL085607 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CUMMINGS, RICHARD D, MCEVER, RODGER PAUL · 2006 to 2015
$16.8M
TR&D3. Approaches to Proteoglycan Function at Biochemical and Cellular LevelsP41GM103390 · NIGMS · UNIVERSITY OF GEORGIA · PI MOREMEN, KELLEY W. · 2012 to 2019
$14.5M
Outside-in Mechanotransduced Inflammatory TargetsR01AI047294 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI SIMON, SCOTT IRWIN · 1999 to 2021
$7.0M
Overall Priority Score P41GM103694 · NIGMS · EMORY UNIVERSITY · PI CUMMINGS, RICHARD D · 2013 to 2018
$6.9M
Molecularly Engineered Blockade of Islet Induced Inflammatory ResponsesR01DK069275 · NIDDK · EMORY UNIVERSITY · PI CHAIKOF, ELLIOT · 2004 to 2013
$3.2M
Facile Synthesis of Glycosulfopeptides and Related BioconjugatesU01GM116196 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT, CUMMINGS, RICHARD D · 2015 to 2018
$2.6M
A PSGL-1 Glycopeptide Mimetic for Treatment of Venous ThromboembolismR01HL128237 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2015 to 2018
$1.7M
Integrating Experiment and Theory to Characterize Diagnostic Antibody SpecificityR01GM094919 · NIGMS · UNIVERSITY OF GEORGIA · PI WOODS, ROBERT J · 2010 to 2013
$1.7M
Site-Specific Therapies To Prevent Intimal HyperplasiaR01HL106018 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHAIKOF, ELLIOT · 2011 to 2014
$1.6M
NHLBI NIH HHS HL085607NHLBI NIH HHS HL106018NHLBI NIH HHS HL60963NHLBI NIH HHS P01 HL085607NHLBI NIH HHS R01 HL106018NHLBI NIH HHS R01 HL128237NIAID NIH HHS AI047294NIAID NIH HHS R01 AI047294NIDDK NIH HHS DK069275NIDDK NIH HHS R01 DK069275NIGMS NIH HHS GM094919NIGMS NIH HHS GM103390NIGMS NIH HHS GM103694NIGMS NIH HHS P41 GM103390NIGMS NIH HHS P41 GM103694NIGMS NIH HHS R01 GM094919NIGMS NIH HHS U01 GM116196
6 · The paper itself

Abstract

Blockade of P-selectin (P-sel)/PSGL-1 interactions holds significant potential for treatment of disorders of innate immunity, thrombosis and cancer. Current inhibitors remain limited due to low binding affinity or by the recognized disadvantages inherent to chronic administration of antibody therapeutics. Here we report an efficient approach for generating glycosulfopeptide mimics of N-terminal PSGL-1 through development of a stereoselective route for multi-gram scale synthesis of the C2 O-glycan building block and replacement of hydrolytically labile tyrosine sulfates with isosteric sulfonate analogues. Library screening afforded a compound of exceptional stability, GSnP-6, that binds to human P-sel with nanomolar affinity (Kd~22 nM). Molecular dynamics simulation defines the origin of this affinity in terms of a number of critical structural contributions. GSnP-6 potently blocks P-sel/PSGL-1 interactions in vitro and in vivo and represents a promising candidate for the treatment of diseases driven by acute and chronic inflammation.

Indexed as

AnimalsBlood PlateletsCell AdhesionCell AggregationCell LineE-SelectinFlow CytometryGlycopeptidesHumansIn Vitro TechniquesLeukocytesL-SelectinMaleMembrane GlycoproteinsMiceMolecular Dynamics SimulationE-SelectinGlycopeptidesL-SelectinMembrane GlycoproteinsP-SelectinP-selectin ligand protein

Identifiers

PMID25824568
PMCPMC4423566
OpenAlexW2030476868

What Socratic holds

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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 Socratic graph.