Synthesis and Biological Evaluation of alpha-Galactosylceramide Analogues with Heteroaromatic Rings and Varying Positions of a Phenyl Group in the Sphingosine Backbone
- Authors
- 김용주
- Issue Date
- 9월-2013
- Publisher
- AMER CHEMICAL SOC
- Citation
- JOURNAL OF MEDICINAL CHEMISTRY, v.56, no.17, pp.7100 - 7109
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF MEDICINAL CHEMISTRY
- Volume
- 56
- Number
- 17
- Start Page
- 7100
- End Page
- 7109
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/139992
- DOI
- 10.1021/jm400949h
- ISSN
- 00222623
- Abstract
- We designed and synthesized seven alpha-GalCer analogues with a pyrazole moiety and varying positions of a phenyl group in the sphingosine backbone to polarize cytokine secretion. On the basis of in vitro and in vivo biological evaluations, we found that analogue 5 induced greater polarization toward Th2 and greater secretion of the immunomodulatory cytokine, IL-4, over secretion of pro-inflammatory cytokines, IFN-gamma and IL-17. Treatment of a single dose of analogue 5 markedly ameliorated disease pathogenesis in an animal model of an inflammatory demyelinating disease of the central nervous system, compared to that of KRN7000 (1). Therefore, this new alpha-GalCer analogue 5 is a novel iNKT ligand that stimulates the selective secretion of anti-inflammatory cytokines and regulates autoimmune diseases by reducing Th1 and Th17 responses.
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