title: Detection of tumor-associated glycopeptides by lectins: the peptide context modulates carbohydrate recognition.
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.
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Madariaga
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Sáez
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Víctor J
authors.initials: VJ
authors.lastname: Somovilla
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Coelho
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Jessika
authors.initials: J
authors.lastname: Valero-González
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro-López
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Asensio
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Jesús H
authors.initials: JH
authors.lastname: Busto
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Avenoza
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Filipa
authors.initials: F
authors.lastname: Marcelo
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Hurtado-Guerrero
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Corzana
authors.affiliation: Centro de Investigación en Síntesis Química, Departamento de Química, Universidad de La Rioja, E-26006 Logroño, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Peregrina
mesh_terms: D000595:Amino Acid Sequence; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D002240:Carbohydrate Sequence; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006020:Glycopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry* / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D006020:Glycopeptides; D037102:Lectins; C060192:MUC1 protein, human; D018396:Mucin-1; D010446:Peptide Fragments; C040286:Tn antigen