From a historical perspective, no single class of organic compounds has shared the same impact on the evolution of stereochemistry as sugar molecules.
A renaissance period for sugars is in full swing with the creation of new subdisciplines that bridge chemistry and biology. Sugar chemistry has emerged as a pivotal link between molecular recognition and biological events in conjunction with vital life processes.
The preceding preamble to a sugar chemistry panorama was necessary to introduce this PhD work, based on glycochemistry, that has been planned, developed and realized paying attention to the biological impact of each synthesized compound. A common aspect, as indicates in the title “synthesis of immunologically relevant PAMAM-based glycodendrimers”, is the preparation of oligosaccharide and their mimic structures which have been loaded on multibranched molecules (PAMAM dendrons) tested or to be tested towards immune system .
In Part 1 (Section 1 & 2) is described the preparation of PAMAM based glyconjugates that might be used as vaccines against pneumococcal diseases, a worldwide pathogenic problem. Starting from commercial available products as lactose and glucosamine, multistep sequences, characterized by higly regio- and stereoselective reactions, have permitted to obtain two oligosaccharides, that represent the repeating units of two different Streptococcus Pneumoniae capsular polysaccharides serotype 14 and 19F. Both oligosaccharides have a functionalized spacer on anomeric position that permits the conjugation with dendritic matrices or directly with immunogenic proteins.
In Part 2 is presented the synthesis of various 1-deoxynojirimycin (DNJ) based iminosugars as activators of Natural Killer cells, lymphoid cells that represent an important protection against pathogenic agents. A common structural aspect is the presence of an N-acetylhexosaminyl unit beta (1->4) linked with the most studied iminosugar, the DNJ.
Two representatives of this compound family have been tested towards NKR-P1 and CD69 receptors and the most relevant result has been the NK stimulation action of DNJ itself. This study on NK carbohydrate ligand has been completed by the preparation of various PAMAM glycodendrimers loaded with NK cell activators to be tested in a multivalence effect study
