溶血磷脂酰胆碱衍生物的合成及其对自然杀伤T细胞的激活作用
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摘要
溶血磷脂酰乙醇胺(pLPE)是自然杀伤T细胞(NKT)的内源性抗原。溶血磷脂酰胆碱衍生物(LPC)与CD1d结合被NKT细胞识别并激活NKT细胞。本文以手性甘油醇缩丙酮为起始原料,合成了LPC衍生物(5和6),其结构经~1H NMR,~(13)C NMR,~(31)P NMR和HR-MS(ESI)确证。研究了5和6的免疫活性。结果表明:100 ng·mL~(-1)6负载mCD1d分子后可刺激2H4细胞释放IL-2因子(32.13±1.56 pg·mL~(-1)),具有潜在的NKT激活性质。
Plasmalogen lysophosphatidylethanolamines(pLPE), had been found as self antigens for natural killer T cells(NKT cells). Lysophosphatidylcholines(LPC) was reported to be recognized by NKT cells as antigens presented by CD1 d. Two LPC derivatives(5 and 6) were synthesized using 2,3-O-isopropylidene-sn-glycerol as material. The structures were confirmed by ~1H NMR, ~(13)C NMR, ~(31)P NMR and HR-MS(ESI). The immunocompetence of 5 and 6 were investigated. The results showed that 100 ng·mL~(-1)6 loaded with plate-bound mCD1 d stimulated NKT 2 H4 cells to release IL-2(32.13±1.56 pg·mL~(-1)). The compound 6 was a potential new NKT agonist.
Plasmalogen lysophosphatidylethanolamines(pLPE), had been found as self antigens for natural killer T cells(NKT cells). Lysophosphatidylcholines(LPC) was reported to be recognized by NKT cells as antigens presented by CD1 d. Two LPC derivatives(5 and 6) were synthesized using 2,3-O-isopropylidene-sn-glycerol as material. The structures were confirmed by ~1H NMR, ~(13)C NMR, ~(31)P NMR and HR-MS(ESI). The immunocompetence of 5 and 6 were investigated. The results showed that 100 ng·mL~(-1)6 loaded with plate-bound mCD1 d stimulated NKT 2 H4 cells to release IL-2(32.13±1.56 pg·mL~(-1)). The compound 6 was a potential new NKT agonist.
引文
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[17] 冯俊娜,高芳,彭绍辉,等. KRN7000结构类似物及其免疫活性研究进展[J].有机化学,2015,35(5):997-1008.
[2] BENDELAC A, SAVAGE P B, TEYTON L. The biology of NKT cells[J].Annu Rev Immunol,2007,25(1):297-336.
[3] GODFREY D I, STANKOVIC S, BAXTER A G. Raising the NKT cell family[J].Nat Immunol,2010,11(3):197-206.
[4] BERZINS S P, SMYTH M J, BAXTER A G. Presumed guilty:Natural killer T cell defects and human disease[J].Nat Rev Immunol,2011,11(2):131-142.
[5] GAPIN L, GODFREY D I, ROSSJOHN J. Natural killer T cell obsession with self-antigens[J].Curr Opin Immunol,2013,25(2):168-173.
[6] BORG N A, WUN K S, KJER N L, et al. CD1d-lipid-antigen recognition by the semi-invariant NKT T-cell receptor[J].Nature,2007,448(7149):44-49.
[7] GODFREY D I, PELLICCI D G, PATEL O, et al. Antigen recognition by CD1d-restricted NKT T cell receptors[J].Semin Immunol,2010,22(2):61-67.
[8] VENKATASWAMY M M, PORCELLI S A. Lipid and glycolipid antigens of CD1d-restricted natural killer T cells[J].Semin Immunol,2010,22(2):68-78.
[9] FACCIOTTI F, RAMANJANEYULU G S, LEPORE M, et al. Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus[J].Nat Immunol,2012,13(5):474-480.
[10] BRUTKIEWICZ R R, DENT A L. Lipids-[YAcy]-Us:Peroxisome generation of iNKT ligands[J].Nat Immunol,2012,13(5):435-436.
[11] NI G, LI Z, LIANG K, et al. Synthesis and evaluation of immunostimulant plasmalogen lysophosphatidylethanolamine and analogues for natural killer T cells[J].Bioorganic & Medicinal Chemistry,2014,22(11):2966-2973.
[12] CERUNDOLO V, FOX L M, COX D G, et al. Recognition of Lyso-phospholipids by human natural killer T lymphocytes[J].PLoS Biology,2009,7(10):e1000228.
[13] DUMOULIN F, LAFONT D, BOULLANGER P, et al. Self-organizing properties of natural and related synthetic glycolipids[J].J Am Chem Soc,2002,124(46):13737-13748.
[14] SUTTER M, DAYOUB W, METAY E, et al. 1-O-alkyl (di)glycerol ethers synthesis from methyl esters and triglycerides by two pathways:Catalytic reductive alkylation and transesterification/reduction[J].Green Chem,2013,15(3):786-797.
[15] MAGNUSSON C D, GUDMUNDSDOTTIR A V, HARALDSSON G G. Chemoenzymatic synthesis of a focused library of enantiopure structured 1-O-alkyl-2,3-diacyl-sn-glycerol type ether lipids[J].Tetrahedron,2011,67(10):1821-1836.
[16] NAIDENKO O V, MAHER J K, ERNST W A, et al. Binding and antigen presentation of ceramide-containing glycolipids by soluble mouse and human CD1d molecules[J].Journal of Experimental Medicine,1999,190(8):1069-1079.
[17] 冯俊娜,高芳,彭绍辉,等. KRN7000结构类似物及其免疫活性研究进展[J].有机化学,2015,35(5):997-1008.