209899-67-2Relevant academic research and scientific papers
An efficient synthesis of a 6″-BODIPY-α-Galactosylceramide probe for monitoring α-Galactosylceramide uptake by cells
Cheng, Janice M.H.,Chee, Stephanie H.,D?len, Yusuf,Verdoes, Martijn,Timmer, Mattie S.M.,Stocker, Bridget L.
, (2019/11/05)
Herein, an efficient synthesis of BODIPY-α-Galactosylceramide 3, which can be used to study the cellular uptake of the potent immunostimulatory parent compound α-Galactosylceramide, is reported. Key in our synthetic strategy is the six-step synthesis of the core BODIPY scaffold (64% yield overall) and its quantitative conversion to an N-hydroxysuccinimidyl ester to facilitate conjugation and purification of the target glycolipid. For the preparation of the core of the glycolipid, the solubility of the lipid acceptor proved to be critical. The ability of BODIPY-αGalCer 3 to activate invariant natural killer cells was then demonstrated in vitro.
Synthesis and biological activities of 5-thio-α-GALCERS
Bi, Jingjing,Wang, Jing,Zhou, Kai,Wang, Yuancheng,Fang, Min,Du, Yuguo
, p. 476 - 480 (2015/04/27)
NKT cells, a unique subset of T cells that recognizes glycolipid antigens presented by CD1d molecules, are believed to produce key cytokines of both Th1 and Th2 T cells and are thus involved in the control of several types of immune response. As an active glycolipid antigen having α-galactosyl ceramide core structure, KRN7000 showed promising immunostimulation activity and was selected as an anticancer drug candidate for further clinical application. In this report, three new KRN7000 structural analogues were designed and synthesized, in which the ring oxygen of the galactopyranose residue is replaced by a sulfur atom along with the variation on the lipid chain. Their abilities for stimulating mouse NKT cells to produce IFN-γ and IL-4 were evaluated both in vivo and in vitro.
Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3)
Xia, Chengfeng,Yao, Qingjia,Schuemann, Jens,Rossy, Emmanuel,Chen, Wenlan,Zhu, Lizhi,Zhang, Wenpeng,De Libero, Gennaro,Wang, Peng George
, p. 2195 - 2199 (2007/10/03)
Glycoceramides can activate NKT cells by binding with CD1d to produce IFN-γ, IL-4, and other cytokines. An efficient synthetic pathway for α-galactosylceramide (KRN7000) was established by coupling a protected galactose donor to a properly protected ceramide. During the investigation, it was discovered that when the ceramide was protected with benzyl groups, only β-galactosylceramide was produced from the glycosylation reaction. In contrast, the ceramide with benzoyl protecting groups produced α-galactosylceramide. Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Galα1-3Galβ1-4Glc donor with 2-azido-sphingosine in high yield. Biological assays on the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell clones or hybridomas.
Structure-activity relationship of α-galactosylceramides against b16- bearing mice
Morita,Motoki,Akimoto,Natori,Sakai,Sawa,Yamaji,Koezuka,Kobayashi,Fukushima
, p. 2176 - 2187 (2007/10/02)
Agelasphin-9b, (2S,3S,4R)-1-O-(α-D-galactopyranosyl)-16-methyl-2-[N- ((R)-2-hydroxytetracosanoyl)-amino]-1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(α- D-galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol, was selected as a candidate for clinical application.
