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.
Keyphrases
- molecular docking
- immune response
- molecular dynamics simulations
- fatty acid
- induced apoptosis
- dendritic cells
- cell cycle arrest
- toll like receptor
- regulatory t cells
- single cell
- quantum dots
- high fat diet induced
- endoplasmic reticulum stress
- signaling pathway
- type diabetes
- pseudomonas aeruginosa
- cell death
- metabolic syndrome
- inflammatory response
- highly efficient
- wild type
- metal organic framework
- pi k akt