Topological Requirements for CI-M6PR-Mediated Cell Uptake

Bioconjug Chem. 2019 Oct 16;30(10):2533-2538. doi: 10.1021/acs.bioconjchem.9b00590. Epub 2019 Sep 26.

Abstract

The 300 kDa cation-independent M6P receptor (CI-MPR) mediates ligand internalization and trafficking to the endolysosomal compartments. Because of its endocytotic nature, it has been recognized as a promising class of receptors for target component delivery. Its cellular uptake involves the simultaneous binding of two protein units resulting in the formation of receptor dimers. While many multivalent glycoconjugates have been reported to date, little is known about the topological requests to induce an effective recruitment of CI-MPRs. We herein describe the synthesis and cell uptake ability of a set of highly organized glycoclusters bearing one to three saccharide units. The spatial arrangement of carbohydrate ligands is ensured by a heterocyclic γ-peptide central core.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cell Line, Tumor
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Receptor, IGF Type 2 / chemistry
  • Receptor, IGF Type 2 / metabolism*

Substances

  • Receptor, IGF Type 2
  • cation-dependent mannose-6-phosphate receptor