New insights into molecular recognition of epitopes related to MUC1 human mucin by lectins

Tn antigen ( -O-GalNAc-Ser/Thr) is one of the most specific human tumorassociated structures. This motif is implicated in HIV infection and it is expressed early in tumor cells. It has been observed that there is a direct correlation between carcinoma aggressiveness and the density of this antigen. For this reason, Tn determinant is a convenient cancer biomarker. Mucin-like glycopeptides and glycoproteins, in particular MUC1, incorporate this structure in their sequence. While in normal cells this O-glycosylated protein carries complex oligosaccharides, in cancer cells, MUC1 expression is increased and its glycans are short and poorly branched. Therefore, Tn antigen is now exposed to the immune system generating an immunological response. From a structural point of view, Tn antigen is referred to Nacetylgalactosamine (GalNAc) -O-linked to serine (Ser) or threonine (Thr), not discriminating the amino acid to which GalNAc is linked. However, in this Thesis, we have synthesized different representative MUC1 epitopes bearing Ser and Thr in their structure and we have detected differences between these two amino acids in terms of affinity to lectins. As a result, it is important to mention specifically the underlying amino acid in Tn antigen. We have also analyzed the role of flanking amino acids of Tn antigen in the peptide chain, getting surprising results in terms of affinity to lectins. In addition, we have obtained an X-ray structure by the first time of soybean agglutinin (SBA) lectin linked to a MUC1-derived glycopeptide. All these results may have important implications for better understanding the glycopeptide-lectin interactions and may contribute to engineer new binding sites, allowing the design of novel glycosensors for Tn antigen detection in tumor cells.

Grantor dc:publisher

Universidad de La Rioja (España)

Year dc:date

2015

Author dc:creator

• Madariaga Merino, David

Contributors dc:contributor

• Peregrina García, Jesús Manuel (Universidad de La Rioja)
• Corzana López, Francisco (Universidad de La Rioja)

Statement dc:rights

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Language dc:language

eng

Repository record dc:identifier

https://dialnet.unirioja.es/servlet/oaites?codigo=44390

OAI identifier oai:identifier

oai:dialnet.unirioja.es:TES0000007535