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https://hdl.handle.net/1889/1121
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DC Field | Value | Language |
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dc.contributor.advisor | Ungaro, Rocco | - |
dc.contributor.advisor | Casnati, Alessandro | - |
dc.contributor.author | Rispoli, Gabriele | - |
dc.date.accessioned | 2009-06-29T09:23:26Z | - |
dc.date.available | 2009-06-29T09:23:26Z | - |
dc.date.issued | 2009-03-06 | - |
dc.identifier.uri | http://hdl.handle.net/1889/1121 | - |
dc.description.abstract | In the present PhD thesis, new multivalent polyglycosylated ligands able to interact with multimeric proteins such as Lectins were synthesised. Some of these ligands possess a peptide dendrimer scaffold and bear L-Fuc at the periphery for the interaction with the LecB of Pseudomonas Aeruginosa, an opportunistic pathogen that causes a variety of diseases, including respiratory tract infections in patients suffering from cystic fibrosis. Two dendrimers based on L-amino acids and one based on D-amino acids were synthesised using solid-phase peptide synthesis. All these fucosylated dendrimers showed to inhibit the adhesion of LecB to a glycoprotein in an ELLA test, with IC50 values quite close each to the others. The relative potency per sugar units compared to fucose ranges from 4 to 20 clearly indicating that a multivalent effect is operating. Interestingly, the dendrimer based on D-amino acids is much more stable to proteolysis than those derived from L-amino acids both in presence of enzyme (Trypsin or Chymotrypsin) and in the presence of human serum or PAO1 bacterial strains indicating that this derivative has potential in therapeutic applications in vivo. In the second part of the thesis, new potential Site-Directed Contrast Agents for MRI, which exploit the cluster glycoside effect, were synthesised by coupling a tetraacetic acid tetraazadodecane (DOTA) to a polyglycosylated calix[4]arene or gallic acid scaffold. Different synthetic procedures were attempted to introduce glycosyl units especially on the calixarene scaffolds. It was finally found that the best one exploits the “Click Chemistry” approach which leads to triazole formation. On the calix[4]arene scaffold, an azido derivatives was coupled with an alkynylglycoside. In order to release the steric crowding which originates at the upper rim during the glycoconjugation, it was necessary to introduce a three-atom spacer between the macrocycle and the forming triazole units. Both on the calixarene and gallic acid scaffold, the glyconjugation reactions via “Click Chemistry” proceed rather smoothly and in very high yields. The Gd(III) complexes of the ligands based on gallic acid were prepared and their relaxivity properties studied in water solution showing remarkable stability constants. These Gd(III) complexes, thanks to the multivalent display of galactose or glucose units strongly interact with plant lectins such as Concanavalin A (ConA) and PeaNut Agglutinin (PNA) auguring well for their future studies as “Site-Directed Contrast Agents”. | en |
dc.language.iso | Inglese | en |
dc.publisher | Università degli Studi di Parma. Dipartimento di Chimica Organica e Industriale | en |
dc.publisher | Università degli Studi di Parma. Dipartimento di Chimica Generale e Inorganica, Chimica Analitica, Chimica Fisica | en |
dc.relation.ispartofseries | Dottorato di ricerca in Scienze Chimiche | en |
dc.rights | Gabriele Rispoli, ©2009 | en |
dc.subject | Size specific contrast agents | en |
dc.subject | Multivalent ligands | en |
dc.subject | Neoglycoconjugates | en |
dc.subject | Lectin inhibitor | en |
dc.subject | Glycodendrimers | en |
dc.subject | DOTA conjugates | en |
dc.title | Synthesis of multivalent glycoclusters for the selective inhibition of lectins and targeted imaging | en |
dc.type | Doctoral thesis | en |
dc.subject.miur | CHIM/04 | en |
dc.description.fulltext | open | en |
Appears in Collections: | Scienze chimiche. Tesi di dottorato |
Files in This Item:
File | Description | Size | Format | |
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All final.pdf | tesi dottorato completa | 2.95 MB | Adobe PDF | View/Open |
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