RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines

Takuya Tashiro; Ryusuke Nakagawa; Takatsugu Hirokawa; Sayo Inoue; Hiroshi Watarai; Masaru Taniguchi; Kenji Mori

doi:10.1016/j.bmc.2009.07.025

RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines

Takuya Tashiro, Ryusuke Nakagawa, Takatsugu Hirokawa, Sayo Inoue, Hiroshi Watarai, Masaru Taniguchi, Kenji Mori

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-γ, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.

Original language	English
Pages (from-to)	6360-6373
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	17
DOIs	https://doi.org/10.1016/j.bmc.2009.07.025
Publication status	Published - 2009 Sept 1
Externally published	Yes

Keywords

Carbasugar
Cyclitol
KRN7000
NKT cell
α-GalCer

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2009.07.025

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RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000 : Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines. / Tashiro, Takuya; Nakagawa, Ryusuke; Hirokawa, Takatsugu et al.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 17, 01.09.2009, p. 6360-6373.

Research output: Contribution to journal › Article › peer-review

Tashiro, T, Nakagawa, R, Hirokawa, T, Inoue, S, Watarai, H, Taniguchi, M & Mori, K 2009, 'RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines', Bioorganic and Medicinal Chemistry, vol. 17, no. 17, pp. 6360-6373. https://doi.org/10.1016/j.bmc.2009.07.025

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title = "RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines",

abstract = "Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-γ, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.",

keywords = "Carbasugar, Cyclitol, KRN7000, NKT cell, α-GalCer",

author = "Takuya Tashiro and Ryusuke Nakagawa and Takatsugu Hirokawa and Sayo Inoue and Hiroshi Watarai and Masaru Taniguchi and Kenji Mori",

note = "Funding Information: We thank Professor H. Watanabe and Drs. K. Ishigami (the University of Tokyo), K. Fuhshuku (Toyama Prefectural University), and M. Shiozaki (RIKEN RCAI) for their helpful comments. T.T. is grateful to Professor T. Nakata (Science University of Tokyo) for his encouragement. This work was partly supported by Grant-in-Aid for Young Scientists (B) (No. 20790108) to T.T. from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. ",

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AU - Tashiro, Takuya

AU - Nakagawa, Ryusuke

AU - Hirokawa, Takatsugu

AU - Inoue, Sayo

AU - Watarai, Hiroshi

AU - Taniguchi, Masaru

AU - Mori, Kenji

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PY - 2009/9/1

Y1 - 2009/9/1

N2 - Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-γ, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.

AB - Cyclitol [RCAI-37 (1), 59 (5), 92 (7), and 102 (2)] and carbasugar analogs [RCAI-56 (3), 60 (4), and 101 (6)] of KRN7000 were synthesized through coupling reactions of the corresponding cyclitol or carbasugar derivatives with a cyclic sulfamidate (9) as the key step. Bioassay showed RCAI-56 (3, carbagalactose analog of KRN7000), 59 (5, 1-deoxy-neo-inositol analog), and 92 (7, 1-O-methylated 5) to be remarkably potent stimulants of mouse lymphocytes to produce Th1-biased cytokines, such as interferon-γ, in vivo. RCAI-60 (4, carbafucose analog) and RCAI-101 (6, 6-O-methylated 3) showed strong bioactivity, on the other hands, RCAI-37 (1, myo-inositol analog) and 102 (2, neo-inositol analog) induced little cytokine production.

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KW - NKT cell

KW - α-GalCer

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RCAI-37, 56, 59, 60, 92, 101, and 102, cyclitol and carbasugar analogs of KRN7000: Their synthesis and bioactivity for mouse lymphocytes to produce Th1-biased cytokines

Abstract

Keywords

ASJC Scopus subject areas

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