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

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00619643" target="_blank" >RIV/61388963:_____/25:00619643 - isvavai.cz</a>
Alternative codes found
RIV/60461373:22330/25:43932125 RIV/00216208:11310/25:10506220
Result on the web
<a href="https://doi.org/10.1002/chem.202500973" target="_blank" >https://doi.org/10.1002/chem.202500973</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/chem.202500973" target="_blank" >10.1002/chem.202500973</a>

Result language
angličtina
Original language name
Design of Potent Mannose-6-Phosphate Derivatives as Ligands for CI-M6P/IGF2R Using Fluorescence Polarization Assay
Original language description
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 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, alongside 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 affinity 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 CI-M6P/IGF2R domains further elucidated the binding mechanisms, offering new directions for the development of even more effective ligands. This study advances the design of therapeutic strategies that leverage CI-M6P/IGF2R for targeted biomolecule delivery to lysosomes, opening new possibilities for biomedical applications.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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