Synthetic Glycolipids as Molecular Vaccine Adjuvants: Mechanism of Action in Human Cells and In Vivo Activity Abstract Modern adjuvants for vaccine formulations are immunostimulating agents whose action is based on the activation of pattern recognition receptors (PRRs) by well-defined ligands to boost innate and adaptive immune responses. Monophosphoryl lipid A (MPLA), a detoxified analogue of lipid A, is a clinically approved adjuvant that stimulates toll-like receptor 4 (TLR4). The synthesis
Effect of chemical modulation of toll-like receptor 4 in an animal model of ulcerative colitis. Facchini FA, Di Fusco D, Barresi S, Luraghi A, Minotti A, Granucci F, Monteleone G, Peri F, Monteleone I. Abstract PURPOSE: The partial ineffectiveness and side effects of inflammatory bowel disease (IBD) current therapies drive basic research to look for new therapeutic target in order to develop new drug lead. Considering the pivotal role
Read this paper in Sci Reports Abstract: New monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. A panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized with the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding of the synthetic compounds to purified, functional recombinant human MD-2 was studied by four independent methods. All compounds bound to MD-2 with
Read this Open Access paper!
Full Paper Co-administration of Antimicrobial Peptides (AMPs) EnhancesToll-like Receptor 4 (TLR4) Antagonist Activity of a Synthetic Glycolipid Authors Francesco Peri, Fabio Alessandro Facchini, Helena Coelho, Stefania Enza Sestito, Sandra Delgado, Alberto Minotti, David Andreu, Jesús Jiménez-Barbero ChemMedChem Abstract This study describes the effect of co-administration of antimicrobial peptides (AMPs) and synthetic glycolipid FP7, active in inhibiting inflammatory cytokine production caused by TLR4 activation and signaling. The co-administration of two
Int. J. Mol. Sci. 2017, 18(11), 2318; doi:10.3390/ijms18112318 Abstract The interactions between sugar-containing molecules from the bacteria cell wall and pattern recognition receptors (PRR) on the plasma membrane or cytosol of specialized host cells are the first molecular events required for the activation of higher animal’s immune response and inflammation. This review focuses on the role of carbohydrates of bacterial endotoxin (lipopolysaccharide, LPS, lipooligosaccharide, LOS, and lipid A), in the interaction