Detection of Tumor-Associated Glycopeptides by Lectins: The Peptide Context Modulates Carbohydrate Recognition

DOI: 10.1021/cb500855x
PMID: 25457745

Authors: David Madariaga (Universidad de La Rioja) , Nuria Martínez-sáez (Universidad de La Rioja) , Víctor J. Somovilla (Universidad de La Rioja) , Helena Coelho (Universidad de La Rioja) , Jessika Valero-gonzález (Universidad de La Rioja) , Jorge Castro-lópez (Universidad de La Rioja) , Juan L. Asensio (Universidad de La Rioja) , Jesús Jiménez-barbero (Universidad de La Rioja) , Jesús H. Busto (Universidad de La Rioja) , Alberto Avenoza (Universidad de La Rioja) , Filipa Marcelo (Universidad de La Rioja) , Ramón Hurtado-guerrero (Universidad de La Rioja) , Francisco Corzana (Universidad de La Rioja) , Jesús M. Peregrina (Universidad de La Rioja)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Chemical Biology , VOL 10 (3) , PAGES 747 - 756

State: Published (Approved)
Published: December 2014
Diamond Proposal Number(s): 8035

Abstract: Tn antigen (α-O-GalNAc-Ser/Thr) is a convenient cancer biomarker that is recognized by antibodies and lectins. This work yields remarkable results for two plant lectins in terms of epitope recognition and reveals that these receptors show higher affinity for Tn antigen when it is incorporated in the Pro-Asp-Thr-Arg (PDTR) peptide region of mucin MUC1. In contrast, a significant affinity loss is observed when Tn antigen is located in the Ala-His-Gly-Val-Thr-Ser-Ala (AHGVTSA) or Ala-Pro-Gly-Ser-Thr-Ala-Pro (APGSTAP) fragments. Our data indicate that the charged residues, Arg and Asp, present in the PDTR sequence establish noteworthy fundamental interactions with the lectin surface as well as fix the conformation of the peptide backbone, favoring the presentation of the sugar moiety toward the lectin. These results may help to better understand glycopeptide–lectin interactions and may contribute to engineer new binding sites, allowing novel glycosensors for Tn antigen detection to be designed.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 23/11/2015 10:51

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