106567-55-9Relevant academic research and scientific papers
Synthetic Glycolipids as Molecular Vaccine Adjuvants: Mechanism of Action in Human Cells and in Vivo Activity
Facchini, Fabio A.,Minotti, Alberto,Luraghi, Andrea,Romerio, Alessio,Gotri, Nicole,Matamoros-Recio, Alejandra,Iannucci, Andrea,Palmer, Charys,Wang, Guanbo,Ingram, Rebecca,Martin-Santamaria, Sonsoles,Pirianov, Grisha,De Andrea, Marco,Valvano, Miguel A.,Peri, Francesco
, p. 12261 - 12272 (2021)
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 of MPLA poses manufacturing and quality assessment challenges. Bridging this gap, we report here the development and preclinical testing of chemically simplified TLR4 agonists that could sustainably be produced in high purity and on a large scale. Underpinned by computational and biological experiments, we show that synthetic monosaccharide-based molecules (FP compounds) bind to the TLR4/MD-2 dimer with submicromolar affinities stabilizing the active receptor conformation. This results in the activation of MyD88- and TRIF-dependent TLR4 signaling and the NLRP3 inflammasome. FP compounds lack in vivo toxicity and exhibit adjuvant activity by stimulating antibody responses with a potency comparable to MPLA.
Structure-activity relationship in monosaccharide-based toll-like receptor 4 (TLR4) antagonists
, p. 2895 - 2909 (2018)
The structure-activity relationship was investigated in a series of synthetic TLR4 antagonists formed by a glucosamine core linked to two phosphate esters and two linear carbon chains. Molecular modeling showed that the compounds with 10, 12, and 14 carbo
Glycosyl Imidates, 25.- Muramic Acid as Glycosyl Donor and Glycosyl Acceptor
Kinzy, Willy,Schmidt, Richard R.
, p. 407 - 415 (2007/10/02)
From the 3-O-unprotected 2-azido-2-deoxy-D-glucose derivatives 3 and 4 and trifluoromethanesulfonates of (S)-lactate as alkylating agents the muramic acid derivatives 8a-10a were obtained diastereospecifically and in high yields. (S)-2-Chloropropionates afforded mixtures of diastereoisomers in this reaction.The muramic acid derivatives 8a-10a were readily transformed into glycosyl donors and glycosyl acceptors.Deacetalation of compounds 8a and 10a and subsequent selective 6-O-silylation afforded the glycosyl acceptor 11; reaction with α-trichloroacetimidate 14 as glycosyl donor provided the β-connected disaccharide 15-β.Deprotection yielded the disaccharide 19, the basic unit of the cell wall peptidoglycan of bacteria.Selective desilylation of the muramic acid derivative 8a and formation of the α-trichloroacetimidate 28-α provided a good muramic acid glycosyl donor.With various glycosyl acceptors depending on the catalyst and the reaction conditions either β- or α-glycosides and -disaccharides were obtained selectively and in high yields.
