Synthesis and Evaluation of 1,2,3-Triazole Containing Analogues of the Immunostimulant α-GalCer

α-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 α-GalCer analogues in which the lipid chain lengths have been incrementally varied. We found that this isosteric replacement of α-G...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2007-02, Vol.50 (3), p.585-589
Main Authors: Lee, Taeho, Cho, Minjae, Ko, Sung-Youl, Youn, Hyun-Jun, Baek, Dong Jae, Cho, Won-Jea, Kang, Chang-Yuil, Kim, Sanghee
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - chemical synthesis
Adjuvants, Immunologic - chemistry
Adjuvants, Immunologic - pharmacology
Animals
Antigens, CD1 - chemistry
Antigens, CD1d
Biological and medical sciences
Cell Line, Tumor
Coculture Techniques
Galactosylceramides - chemical synthesis
Galactosylceramides - chemistry
Galactosylceramides - pharmacology
Humans
Hybridomas
Immunomodulators
Interferon-gamma - secretion
Interleukin-2 - secretion
Interleukin-4 - secretion
Medical sciences
Mice
Mice, Inbred C57BL
Models, Molecular
Pharmacology. Drug treatments
Rats
Receptors, Antigen, T-Cell - agonists
Spleen - cytology
Structure-Activity Relationship
Th2 Cells - immunology
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
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Summary:α-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 α-GalCer analogues in which the lipid chain lengths have been incrementally varied. We found that this isosteric replacement of α-GalCer's amide moiety with triazole increases the IL-4 versus IFN-γ 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 α-GalCer and exhibit a stronger Th2 cytokine response.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm061243q