Chemoenzymatic Synthesis of Glycopeptides to Explore the Role of Mucin 1 Glycosylation in Cell Adhesion.

Chembiochem

Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.

Published: June 2023

AI Article Synopsis

  • Post-translational modifications, like glycosylation, significantly impact protein functions in both normal and disease states, with mucin 1 (MUC1) showing altered patterns in cancer.
  • Researchers created homogeneously O-glycosylated MUC1 peptides to study their effects on cancer cell adhesion, finding that different glycan structures influence how well cancer cells adhere to surfaces.
  • NMR spectroscopy was used to analyze the peptide structures, showing that variations in adhesion were linked to the specific types and quantities of glycans rather than differences in peptide conformation.

Article Abstract

Post-translational modifications affect protein biology under physiological and pathological conditions. Efficient methods for the preparation of peptides and proteins carrying defined, homogeneous modifications are fundamental tools for investigating these functions. In the case of mucin 1 (MUC1), an altered glycosylation pattern is observed in carcinogenesis. To better understand the role of MUC1 glycosylation in the interactions and adhesion of cancer cells, we prepared a panel of homogeneously O-glycosylated MUC1 peptides by using a quantitative chemoenzymatic approach. Cell-adhesion experiments with MCF-7 cancer cells on surfaces carrying up to six differently glycosylated MUC1 peptides demonstrated that different glycans have a significant impact on adhesion. This finding suggests a distinct role for MUC1 glycosylation patterns in cancer cell migration and/or invasion. To decipher the molecular mechanism for the observed adhesion, we investigated the conformation of the glycosylated MUC1 peptides by NMR spectroscopy. These experiments revealed only minor differences in peptide structure, therefore clearly relating the adhesion behaviour to the type and number of glycans linked to MUC1.

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http://dx.doi.org/10.1002/cbic.202200741DOI Listing

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