145411-41-2Relevant academic research and scientific papers
Synthesis of a 2 -Deoxy-β-GalCer
Thakur, Meena S.,Khurana, Archana,Kronenberg, Mitchell,Howell, Amy R.
, p. 10090 - 10102 (2014)
Structural studies of ternary complexes of CD1d/glycosyl ceramides/iNKT cells and CD1d/sulfatide/sulfatide reactive Type II NKT cells have shown how the polar moieties on the glycolipids interact with both the antigen presenting protein (CD1d) and the T cell receptors. However, these structures alone do not reveal the relative importance of these interactions. This study focuses on the synthesis of the previously unknown 2''-deoxy-β-galactosyl ceramide 2. This glycolipid is also evaluated for its ability to stimulate iNKT cells and sulfatide-reactive Type II NKT cells.
New Paradigm in NKT Cell Antigens: MCS-0208 (2-(Hydroxymethyl)phenylthio-phytoceramide) – an Aryl-Phytoceramide Compound with a Single Hydroxyl Group Stimulates NKT Cells
Borràs-Tudurí, Roser,Alcaide, Anna,Aspeslag, Sandrine,Usero, Lorena,Serra, Carmen,Roura-Mir, Carme,Elewaut, Dirk,Llebaria, Amadeu
, p. 2491 - 2496 (2021)
Natural Killer T (NKT) cells play an important role in the immune response and can be activated by glycolipids presented by CD1d protein. We present MCS-0208, an unprecedented arylthioether-phytoceramide able to induce potent invariant NKT (iNKT) cell activation, notably when tested in human iNKT cells. This arylsphingolipid analog has a simple phenyl group containing a single hydroxyl substituent as a surrogate of the sugar ring. The phenylthioether structure contrasts with α-galactosylceramide (1), the prototypical glycolipid used to induce iNKT cell stimulation, where the galactose 2’-OH and 3’-OH substituents are accepted as the minimal footprint and considered critical for NKT T cell receptor (TCR) recognition. A computational study supports the recognition of aromatic compound by the CD1d and TCR proteins as radically new structures for NKT cell stimulation.
RCAI-133, an N-methylated analogue of KRN7000, activates mouse natural killer T cells to produce Th2-biased cytokines
Tashiro, Takuya,Shigeura, Tomokuni,Shiozaki, Masao,Watarai, Hiroshi,Taniguchi, Masaru,Mori, Kenji
, p. 949 - 955 (2013)
We synthesized seven new analogues of KRN7000: RCAI-133 and 154-159. RCAI-154, 156 and 158 are secondary-amide analogues having a hydroxy, a methyl or two methyl groups at the α-position of a linear C18-acyl chain, respectively. RCAI-155, 157 and 159 are corresponding N-methylated tertiary amide analogues, and RCAI-133 is the N-methylated KRN7000. Among them, a PBS solution of RCAI-133 induced mouse lymphocytes to produce Th2-biasing cytokines in vivo, while RCAI-154-159 showed only weak or almost no immunostimulatory activity. Therefore, N-methylation led the glycolipid to produce predominantly Th2-type cytokines, while acyl α-substitution was detrimental to activity.
Effects of Glycon and Temperature on Self-Assembly Behaviors of α-Galactosyl Ceramide in Water
Hamada, Masahiro,Ihsan, Abu Bin,Koyama, Yasuhito,Miyazaki, Ryo,Nakajima, Noriyuki,Nargis, Mahmuda
, p. 7936 - 7944 (2021)
α-Galactosyl ceramide (GalCer) is an anticancer glycolipid consisting of d-galactose and phytosphingosine-based ceramide. Although the amphiphilic structure of GalCer is expected to form self-associates in water, the self-assembly behaviors of GalCer and its derivatives have not been systematically investigated at this moment in spite of its great importance. The evaluation of morphologies and properties of the associates should open new insights into glycolipid chemistry such as the application of GalCer derivatives to a nanocarrier and the elucidation of the detailed pharmacological mechanism of GalCer. Herein, we show the synthesis of the aglycon fragment (Aglycon) of GalCer and the self-assembly behaviors of both GalCer and Aglycon in water. The critical aggregation concentrations of Aglycon and GalCer were determined using UV-vis spectral measurements at various concentrations. The transmission electron microscopy observations of the aqueous sample solutions indicated that the solution of GalCer includes vesicles, while that of Aglycon comprises giant micelles in the absence of vesicles. The vesicle formation in the solution of GalCer was also confirmed by Triton X-100-triggered dye-release experiments. To reveal the effects of glycon on the self-assembly behaviors in detail, we performed the measurements of dynamic light scattering, temperature-dependence of turbidity, differential scanning calorimetry, and wide-angle X-ray diffraction. The results clarify that the glycon moiety of GalCer has a significant role in the formation inhibition of second associates and the plasticization of the hydrophobe. This work will shed light on the other natural glycosides to evaluate the self-assembly behaviors for supramolecular and pharmacological applications in the near future.
A practical and scalable synthesis of KRN7000 using glycosyl iodide as the glycosyl donor
Zhang, Yang,Guo, Jia,Xu, Xiaoyan,Gao, Qi,Liu, Xianglai,Ding, Ning
, p. 248 - 252 (2020/11/30)
KRN7000 is particularly useful because it is a powerful and specific CD1d agonist and has prompted intense interest in the context of immunology in the past 25 years. Its limited commercial availability and high price has led to the publication of many different syntheses. However, almost all of them focused on the methodology development rather than a scalable synthesis. Herein, we have described a practical and scalable procedure for the synthesis of KRN7000 basing on the glycosyl iodide method. This procedure involves total of eight steps to obtain the highly pure product KNR7000 on gram scale from the commercially available starting materials (d-galactose and the phytosphingosine) with only three column chromatographic purifications.
Synthesis of glycerolipids containing simple linear acyl chains or aromatic rings and evaluation of their Mincle signaling activity
Matsumaru, Takanori,Ikeno, Risa,Shuchi, Yusuke,Iwamatsu, Toshiki,Tadokoro, Takashi,Yamasaki, Sho,Fujimoto, Yukari,Furukawa, Atsushi,Maenaka, Katsumi
supporting information, p. 711 - 714 (2019/02/06)
Mincle, expressed in activated phagocytes, recognizes the lipid ligand to activate the innate immune system. We have synthesized glycerol derivatives possessing simple alkyl chains or aromatic rings and elucidated their structure-activity relationships us
INKT CELL MODULATORS AND METHODS OF USING THE SAME
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Paragraph 0069; 00164, (2013/06/27)
Disclosed herein are α-galactosylceramide (α-GalCer) analogs and compositions thereof, methods of activating invariant Natural Killer T (iNKT) cells using said analogs, methods of treating diseases by activating iNKT cells using said analogs, and combinat
Synthesis of a versatile building block for the preparation of 6-N-derivatized α-galactosyl ceramides: Rapid access to biologically active glycolipids
Jervis, Peter J.,Cox, Liam R.,Besra, Gurdyal S.
supporting information; experimental part, p. 320 - 323 (2011/03/20)
A concise route to the 6-azido-6-deoxy-α-galactosyl-phytosphingosine derivative 9 is reported. Orthogonal protection of the two amino groups allows elaboration of 9 into a range of 6-N-derivatized α-galactosyl ceramides by late-stage introduction of the a
Synthesis of threitol ceramide and [14C]threitol ceramide, non-glycosidic analogues of the potent CD1d antigen α-galactosyl ceramide
Garcia Diaz, Yoel R.,Wojno, Justyna,Cox, Liam R.,Besra, Gurdyal S.
experimental part, p. 747 - 753 (2009/09/25)
The synthesis of threitol ceramide, which is a non-glycosidic analogue of the potent CD1d antigen α-galactosyl ceramide, is described. The synthesis of a 14C-labelled threitol ceramide analogue is also presented. This radiolabelled analogue wil
