138889-07-3Relevant articles and documents
A safe and facile route to imidazole-1-sulfonyl azide as a diazotransfer reagent
Ye, Hui,Liu, Ruihua,Li, Dongmei,Liu, Yonghui,Yuan, Haixin,Guo, Weikang,Zhou, Lifei,Cao, Xuefeng,Tian, Hongqi,Shen, Jie,Wang, Peng George
, p. 18 - 21 (2013)
A facile approach to the diazotransfer reagent of imidazole-1-sulfonyl azide was reported. The procedure was well optimized to clarify potential explosion risks. A high production yield as well as small batch variation was achieved even without careful pretreatment of reagents and solvents. HPLC and NMR methods to monitor the process were provided. These features made this protocol suitable for large scale preparation in academia and industry as well.
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 (2021/09/02)
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
Facchini, Fabio A.,Zaffaroni, Lenny,Minotti, Alberto,Rapisarda, Silvia,Rapisarda, Valentina,Forcella, Matilde,Fusi, Paola,Airoldi, Cristina,Ciaramelli, Carlotta,Billod, Jean-Marc,Schromm, Andra B.,Braun, Harald,Palmer, Charys,Beyaert, Rudi,Lapenta, Fabio,Jerala, Roman,Pirianov, Grisha,Martin-Santamaria, Sonsoles,Peri, Francesco
, p. 2895 - 2909 (2018/04/20)
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
