Synthesis and evaluation of 1,2,3-triazole containing analogues of the immunostimulant alpha-GalCer.
alpha-GalCer is the first defined and most potent agonistic antigen of the T cell receptor of natural killer T cells. We have prepared a series of 1,2,3-triazole-containing alpha-GalCer analogues in which the lipid chain lengths have been incrementally varied. We found that this isosteric replacement of alpha-GalCer's amide moiety with triazole increases the IL-4 versus IFN-gamma bias of released cytokines. The stimulatory effect was influenced by the length of the attached chain. In particular, the long-chained triazole analogues have a comparable stimulatory effect on cytokine production as alpha-GalCer and exhibit a stronger Th2 cytokine response.
Lee
Taeho
T
College of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Korea.
Cho
Minjae
M
Ko
Sung-Youl
SY
Youn
Hyun-Jun
HJ
Baek
Dong Jae
DJ
Cho
Won-Jea
WJ
Kang
Chang-Yuil
CY
Kim
Sanghee
S
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry; D055610:Antigens, CD1d; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006825:Hybridomas; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D013154:Spleen / Q000166:cytology; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000276:immunology; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D005699:Galactosylceramides; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D014230:Triazoles; D015847:Interleukin-4; D007371:Interferon-gamma; C103873:KRN 7000