New glycolipids and a benzylammonium lipid were rationally designed by varying the chemical structure of a D-glucose-derived hit compound active as lipid A antagonist. We report the synthesis of these compounds, their in vitro activity as lipid A antagonists on HEK cells and the capacity to inhibit LPS-induced septic shock in vivo. The lack of toxicity and the good in vivo activity suggest the use of some compounds of the panel as hits for anti-sepsis drug development. In addition in the studies presented in this PhD thesis new classes of natural compounds are tested for their ability to interact with TLR4 receptor complex.
|Data di pubblicazione:||15-dic-2009|
|Titolo:||Synthesis and biological characterization of novel TLR4 ligands|
|Settore Scientifico Disciplinare:||BIO/10 - BIOCHIMICA|
|Corso di dottorato:||BIOTECNOLOGIE INDUSTRIALI - 15R|
|Citazione:||(2009). Synthesis and biological characterization of novel TLR4 ligands. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2009).|
|Parole Chiave:||TLR4, Innate Immunity, Glycolipids, Benzylammonium Lipids, Septic shock, Sepsis, LPS, Lipopolysaccharides|
|Appare nelle tipologie:||07 - Tesi di dottorato Bicocca post 2009|