title: Introduction of aromatic group on 4'-OH of α-GalCer manipulated NKT cell cytokine production.
abstract: The glycosphingolipid α-GalCer has been found to influence mammalian immune system significantly through the natural killer T cells. Unfortunately, the pre-clinical and clinical studies revealed several critical disadvantages that prevented the therapeutic application of α-GalCer in treating cancer and other diseases. Recently, the detailed illustration of the CD1d/α-GalCer/NKT TCR complex crystal structural, together with other latest structural and biological understanding on glycolipid ligands and NKT cells, provided a new platform for developing novel glycolipid ligands with optimized therapeutic effects. Here, we designed a series of novel aromatic group substituted α-GalCer analogues. The biological activity of these analogues was characterized and the results showed the unique substitution group manipulated the immune responses of NKT cells. Computer modeling and simulation study indicated the analogues had unique binding mode when forming CD1d/glycolipid/NKT TCR complex, comparing to original α-GalCer.
authors: Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
authors: Wenpeng
authors: W
authors: Zhang
authors: Chengfeng
authors: C
authors: Xia
authors: Janos
authors: J
authors: Nadas
authors: Wenlan
authors: W
authors: Chen
authors: Li
authors: L
authors: Gu
authors: Peng George
authors: PG
authors: Wang
mesh_terms: D055610:Antigens, CD1d / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D005699:Galactosylceramides / Q000737:chemistry* / Q000494:pharmacology; D006017:Glycolipids; D006801:Humans; D007107:Immune System / Q000187:drug effects; D008024:Ligands; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides; D006017:Glycolipids; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; C493154:alpha-galactosylceramide