Tailored Presentation of Carbohydrates on a Coiled Coil-Based Scaffold for Asialoglycoprotein Receptor Targeting

Elsa Zacco, Julia Hütter, Jason L. Heier, Jeremie Mortier, Peter H. Seeberger, Bernd Lepenies, Beate Koksch

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The coiled-coil folding motif represents an ideal scaffold for the defined presentation of ligands due to the possibility of positioning them at specific distances along the axis. We created a coiled-coil glycopeptide library to characterize the distances between the carbohydrate-binding sites of the asialoglycoprotein receptors (ASGPR) on hepatocytes. The components of the glycopeptide library vary for the number of displayed ligands (galactose), their position on the peptide sequence, and the space between peptide backbone and carbohydrate. We determined the binding of the glycopeptides to the hepatocytes, and we established the optimal distance and orientation of the galactose moieties for interaction with the ASGPR using flow cytometry. We confirmed that the binding occurs through endocytosis mediated by ASGPR via inhibition studies with cytochalasin D; fluorescence microscopy studies display the uptake of the carrier peptides inside the cell. Thus, this study demonstrates that the coiled-coil motif can be used as reliable scaffold for the rational presentation of ligands.
Original languageEnglish
JournalA C S Chemical Biology
Volume10
Issue number9
Pages (from-to)2065-2072
Number of pages8
ISSN1554-8929
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • BIOCHEMISTRY
  • RECOGNITION DOMAIN
  • MODEL PEPTIDES
  • RAT-LIVER
  • BINDING
  • GLYCOSYLATION
  • PROTEINS
  • LIGANDS
  • Biochemistry
  • Molecular Medicine
  • asialoglycoprotein receptor
  • carbohydrate
  • cytochalasin D
  • galactose
  • glycopeptide
  • peptide
  • amino acid sequence
  • Article
  • binding site
  • controlled study
  • endocytosis
  • flow cytometry
  • fluorescence microscopy
  • human
  • human cell
  • liver cell
  • peptide library
  • priority journal

Cite this