Synthetic preparation and immunological evaluation of β-mannosylceramide and related <i>N</i>-acyl analogues

Robinson, Sage; Yau, Jessica; Terabe, Masaki; Berzofsky, Jay A.; Painter, Gavin F.; Compton, Benjamin J.; Larsen, David S.

doi:10.1039/d0ob00223b

Cited by 4 publications

(4 citation statements)

References 40 publications

(39 reference statements)

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“…The effective oxidative one-step linking of axially configured 2-O-PMB ether to produce a corresponding p-methoxybenzylidene mixed acetal at the 2-O-position of the mannosy donor with the acceptor as an aglycone. For this method to be more versatile, suitable stabilization of the mixed acetal intermediate by introducing the 2-naphthylidene acetal (Ishiwata et al, 2008b;reviews, Ishiwata et al, 2010b;Ishiwata and Ito, 2012) has been developed for various 1,2-cis linkages for application to the synthesis of plant β-L-arabinofuranosides (Figure 2C3) (Kaeothip et al, 2013a;Kaeothip et al, 2013b;Ishiwata et al, 2014;Ishiwata et al, 2022) and various other types of glycosides Tamigney et al, 2014;Robinson et al, 2020) including β-L-rhamnosyl linkage (Lee et al, 2008;Yu et al, 2016;recent review, Rai and Kulkarni, 2021).…”

Section: Recent Examples Using Intramolecular Coupling For 12-cis Gly...mentioning

confidence: 99%

Recent advances in stereoselective 1,2-cis-O-glycosylations

Ishiwata

Tanaka

et al. 2022

Front. Chem.

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For the stereoselective assembly of bioactive glycans with various functions, 1,2-cis-O-glycosylation is one of the most essential issues in synthetic carbohydrate chemistry. The cis-configured O-glycosidic linkages to the substituents at two positions of the non-reducing side residue of the glycosides such as α-glucopyranoside, α-galactopyranoside, β-mannopyranoside, β-arabinofuranoside, and other rather rare glycosides are found in natural glycans, including glycoconjugate (glycoproteins, glycolipids, proteoglycans, and microbial polysaccharides) and glycoside natural products. The way to 1,2-trans isomers is well sophisticated by using the effect of neighboring group participation from the most effective and kinetically favored C-2 substituent such as an acyl group, although high stereoselective synthesis of 1,2-cis glycosides without formation of 1,2-trans isomers is far less straightforward. Although the key factors that control the stereoselectivity of glycosylation are largely understood since chemical glycosylation was considered to be one of the useful methods to obtain glycosidic linkages as the alternative way of isolation from natural sources, strictly controlled formation of these 1,2-cis glycosides is generally difficult. This minireview introduces some of the recent advances in the development of 1,2-cis selective glycosylations, including the quite recent developments in glycosyl donor modification, reaction conditions, and methods for activation of intermolecular glycosylation, including the bimodal glycosylation strategy for 1,2-cis and 1,2-trans glycosides, as well as intramolecular glycosylations, including recent applications of NAP-ether-mediated intramolecular aglycon delivery.

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Section: Recent Examples Using Intramolecular Coupling For 12-cis Gly...mentioning

confidence: 99%

Recent advances in stereoselective 1,2-cis-O-glycosylations

Ishiwata

Tanaka

et al. 2022

Front. Chem.

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“…Thus, it is highly likely that different species of glycosphingolipid have different activity against NKT cells. However, such a structure–function study of antigens for NKT cells conducted for species other than α-GalCer are very limited, and the information obtained from α-GalCer may not be applicable to other glycosphingolipids [ 182 , 183 ]. Thus, detailed lipid profiling and the examination of antigenic activity of each lipid species are required to understand the function of NKT cells in glioma.…”

Section: Further Questions Regarding Nkt Cells In Gbm Immunitymentioning

confidence: 99%

The Role of NKT Cells in Glioblastoma

Brettschneider

Terabe

2021

Cells

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Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

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“…26,27 Notably, 7DW8-5 (2) and C34 (3) have a stronger binding affinity of CD1d and promote the release of Th1 cytokines, which both exhibited stronger antitumor and antiviral effects and were regarded as promising immune adjuvants. 5,11,28−31 Modifications of 7DW8-5 and C34 have attracted widespread attention to further improve their biological activities, including altering the galactosyl moiety 32,33 and aromatic rings. 34 However, biological activities of phenyl glycolipids with thio-modifications at the acyl moiety remain unknown.…”

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confidence: 99%

“…Modifications of 7DW8-5 and C34 have attracted widespread attention to further improve their biological activities, including altering the galactosyl moiety , and aromatic rings . However, biological activities of phenyl glycolipids with thio-modifications at the acyl moiety remain unknown.…”

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confidence: 99%

Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety

Hao,

Mi,

Chu

et al. 2024

ACS Med. Chem. Lett.

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α-Galactosylceramide (KRN7000 or α-GalCer) analogues terminated with phenyl (Ph) groups at the acyl moiety possess more potency than KRN7000 to activate invariant natural killer T (iNKT) cells for inducing a T helper 1 (Th1)-biased immune response. However, biological activities of phenyl glycolipids with thio-modifications at the acyl moiety remain unknown, and facile approaches for highly stereoselective synthesis of KRN7000 and its analogues are rather scarce. Herein, we exploited 4,6-di-O-tert-butylsilylene (DTBS)-directed stereospecific galactosylation to efficiently synthesize various α-GalCer analogues bearing thioamide, terminal thiophenyl and dual modifications at the acyl moiety. Biological evaluations suggest that a new analogue S34 featuring a terminal Ph-S-Ph-F group exhibits a more superior Th1-biased immune response in mice. Molecular docking analysis revealed that the introduction of a sulfur atom influences vital hydrogen bonding interactions between glycolipids and the cluster of differentiation 1d (CDld), thus adjusting the stability of the glycolipid-CDld complex.

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Synthetic preparation and immunological evaluation of β-mannosylceramide and related N-acyl analogues

Abstract: The synthesis of the invariant natural killer (iNK) T cell agonist β-mannosylceramide along with a series of fatty amide analogues is reported.

Cited by 4 publications

References 40 publications

Recent advances in stereoselective 1,2-cis-O-glycosylations

Recent advances in stereoselective 1,2-cis-O-glycosylations

The Role of NKT Cells in Glioblastoma

Stereospecific Synthesis and Biological Evaluation of KRN7000 Analogues with Thio-modifications at the Acyl Moiety

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