Síntesis y análisis conformacional de glicopéptidos que incorporan ß-glucosa y a-N-acetilgalactosamina
In the last two decades, the glycobiology field, which comprises the study of carbohydrates, glycopeptides and glycoproteins, has attracted considerable attention due to these molecules are involved in many fundamental processes of the life. One of these processes is known as molecular recognition o...
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| Formato: | text (thesis) |
| Lenguaje: | spa |
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Universidad de La Rioja (España)
2014
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| Acceso en línea: | https://dialnet.unirioja.es/servlet/oaites?codigo=44163 |
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| Sumario: | In the last two decades, the glycobiology field, which comprises the study of
carbohydrates, glycopeptides and glycoproteins, has attracted considerable
attention due to these molecules are involved in many fundamental
processes of the life. One of these processes is known as molecular
recognition of ligands by receptors. In particular, this interaction is tightly
related to the 3D structure they adopt.
In this context, this Thesis focuses on searching new non?natural
glycosylamino acids that display different conformations from those that
adopt glycosylated natural amino acids. In this sense, several glycosylamino
acids have been synthesized, which incorporate ?,??disubstituted amino
acids. The structural preferences of these new compounds were elucidated,
combining NMR experiments and Molecular Dynamics simulations. As a
result, the synthetic modifications made in the amino acid moiety can be
regarded as a tool to develop glycosylated derivatives with conformations a
la cartè.
Another issue which this Thesis focuses on, is to find out why glucose only
appear linked to serine, when it is incorporated in a certain peptide sequence
(consensus sequence). In particular, in this work, we studied the consensus
sequence for ??O?glycosylation with glucose. For this purpose, two peptides
and one glycopeptide were synthesized. As a first approaching, we calculated
the spatial distribution of the hydroxyl group of serine, that later will be
glycosylated, and interestingly it is exposed to the solvent, therefore the
glycosylation would be easier.
On the other hand, this Thesis tries to shed some light to the controversial
about the role that peptide moiety plays in the molecular recognition of
glycopeptides by lectins. In this regard, two glycine rich glycopeptides were
synthesized, Gly?Gly?Xxx?Gly?Gly, where Xxx was replaced by Thr/Ser(??OGalNac).
Besides, conformational studies both in the free and bound?states were developed. In addition, thermodynamic parameters corresponding to
molecular recognition of each glycopeptides by two specific lectins were
obtained by microcalorimetry. All this work shows the importance of the
amino acid linked to the carbohydrate plays in the molecular recognition
process. In fact, it is not a mere spectator but it develops a role as modulator
agent. |
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