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....
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| Formato: | text (thesis) |
| Lenguaje: | eng |
| Publicado: |
Universidad de La Rioja (España)
2015
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| Acceso en línea: | https://dialnet.unirioja.es/servlet/oaites?codigo=44390 |
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| Sumario: | 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. |
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