Synthesis and evaluation of immunostimulant plasmalogen lysophosphatidylethanolamine and analogues for natural killer T cells.
Plasmalogen lysophosphatidylethanolamine (pLPE) had been identified as a self antigen for natural killer T cells (NKT cells). It is very important in the development, maturation and activation of NKT cells in thymus. Besides, pLPE is a novel type of antigen for NKT cells. To evaluate the structure-activity relationship (SAR) of this new antigen, pLPE and its analogues referred to different aliphatic chains and linkages at the sn-1 position of the glycerol backbone were synthesized, and the biological activities of these analogues was characterized. It is discovered that the linkages between phosphate and lipid moiety are not important for the antigens' activities. The pLPE analogues 1, 3, 4, 7 and 9, which have additional double bonds on lipid parts, were identified as new NKT agonists. Moreover, the analogues 4, 7 and 9 were discovered as potent Th2 activators for NKT cells.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Guanghui
G
Ni
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Zhiyuan
Z
Li
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Kangjiang
K
Liang
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
Ting
T
Wu
Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.
Gennaro
G
De Libero
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: xiachengfeng@mail.kib.ac.cn.
Chengfeng
C
Xia
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007694:Killer Cells, Natural / Q000187:drug effects*; D008246:Lysophospholipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008968:Molecular Conformation; D010955:Plasmalogens / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D008246:Lysophospholipids; D010955:Plasmalogens; C008301:lysophosphatidylethanolamine
Antigen, lysophospholipids; NKT cells; SAR