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

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 phosphon

SUBMITTER: Mrazkova L 

PROVIDER: S-EPMC12284618 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature