Evidence map›Paper›PMID 40356531›Full record

ArticleChemistry (Weinheim an der Bergstrasse, Germany)2025

Design of Potent Mannose-6-Phosphate Derivatives as Ligands for CI-M6P/IGF2R Using Fluorescence Polarization Assay.

Lucie Mrázková, Klaudia Hladoníková, Barbora Toncarová, Michal Fischer, Jakub Zýka, Jaroslav Kozák, Michal Kráľ, Milan Kožíšek, Jiří Jiráček, Jakub Kaminský and 2 more

Abstract read
In one paragraph

Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

12 authors.

Lucie MrázkováInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0009-0006-4972-8758
Klaudia HladoníkováInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.
Barbora ToncarováThe Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague, 166 28, Czech Republic.
Michal FischerThe Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague, 166 28, Czech Republic.
Jakub ZýkaThe Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague, 166 28, Czech Republic.ORCID https://orcid.org/0000-0002-8944-6169
Jaroslav KozákInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0002-2490-5280
Michal KráľInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0003-0334-9569
Milan KožíšekInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0002-9476-3409
Jiří JiráčekInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0003-3848-2773
Jakub KaminskýInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0001-6347-3022
Kamil ParkanThe Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, Prague, 166 28, Czech Republic.ORCID https://orcid.org/0000-0001-7585-6004
Lenka ŽákováInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo náměstí 542/2, Prague, 160 00, Czech Republic.ORCID https://orcid.org/0000-0001-6439-2574

Funding

Czech Academy of SciencesGrantová Agentura České Republiky 23-05805SMinisterstvo Školství, Mládeže a Tělovýchovy 90254Vysoká Škola Chemicko-technologická v Praze A1 FPBT 2024 003
6 · The paper itself

Abstract

The cation-independent mannose-6-phosphate/IGF2 receptor (CI-M6P/IGF2R) plays a crucial role in transporting lysosomal enzymes and other ligands. In this study, we designed and synthesized novel stable mannose-6-phosphate (M6P) derivatives to enhance their affinity for CI-M6P/IGF2R. To evaluate the binding potency, we employed a sensitive and cost-effective fluorescence polarization assay, enabling rapid quantification of receptor-ligand interactions in solution. The tested compounds included di-, tri-, and penta-M6P peptides along with various M6P-derived small molecules featuring phosphate isosteres or other functional modifications. Our findings indicate that ligands bearing multiple M6P moieties exhibit significantly higher receptor affinities than monomeric compounds and that phosphonate groups may serve as a more stable and potent alternative to native M6P. Computational modeling of ligand interactions with the CI-M6P/IGF2R domains further elucidated the binding mechanisms, offering new directions for the development of more effective ligands. This study advances the design of therapeutic strategies that leverage CI-M6P/IGF2R for targeted biomolecule delivery to lysosomes, thereby opening new possibilities for biomedical applications.

Indexed as

MannosephosphatesReceptor, IGF Type 2Drug DesignFluorescence PolarizationHumansLigandsLysosomesProtein BindingIGF2R protein, humanLigandsmannose-6-phosphateMannosephosphatesReceptor, IGF Type 2fluorescence polarization assayIGF2ligand bindingMannose‐6‐phosphatereceptor

Identifiers

PMID40356531
PMCPMC12284618

What OpenQuestion 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 OpenQuestion graph.