Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs

Tadayori Shimizu, Yoshihisa Iwamoto, Yasutake Yanagihara, Kazuo Ryoyama, Yoshitomo Suhara, Kiyoshi Ikeda, Kazuo Achiwa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The mitogenicity, lethal toxicity, induction of tumor necrosis factor (TNF), production of nitric oxide (NO) and antitumor activity against Meth A fibrosarcoma by chemically synthesized N-acylated asparagine-linked (A-701, A-702 and A-703) or N-acylated serine-linked (A-607) nonphosphorylated acylglucosamine and 4-O-phosphorylated acylglucosamine (A-103) derived lipid A analogs were determined. Compound A-607 (with tetradecanoyl and (R)-3-tetradecanoyloxyterradecanoyl at the C-2 and C-3 positions) induced a significant incorporation of 3H-thymidine into splenocytes of C3H/He mice at concentrations ranging from 3.13 to 50 μM, but the mitogenic activity of A-701 (2-N-acetylglucosamine), A-702 (tetradecanoyl at the C-2), and A-703 (with (R)-tetradecanoyloxytetradecanoyl and tetradecanoyl at the C-2 and C-3) was very weak. The lethality of A-703 and A-103 (with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 and C-3) was weaker than that of A-607 at doses of 300 and 750 nmol/kg in C57BL/6 mice loaded with D-galactosamine. Peritoneal macrophages, stimulated with A-701-A-703, caused production of TNF which induce L929 cell lysis in vitro, and A-703 showed a high production of TNF. The compounds, except for A-607, exhibited little NO production by macrophages, but did induce the NO production in the presence of interferon gamma. Induction of TNF and NO inducible activity by A-703 was lower than that of A-607. A-703, A-607 and A-103 showed antitumor activity against Meth A fibrosarcoma in BALB/c mice. When A-703 or A-103 with muramyl dipeptide was administered, A-703 failed to show combined effects, but A-103 did. We concluded from these findings that the biological potency of asparagine compounds appears to be placed between serine- and amino-free compounds.

Original languageEnglish
Pages (from-to)321-331
Number of pages11
JournalImmunobiology
Volume196
Issue number4
Publication statusPublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Cite this

Shimizu, T., Iwamoto, Y., Yanagihara, Y., Ryoyama, K., Suhara, Y., Ikeda, K., & Achiwa, K. (1996). Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs. Immunobiology, 196(4), 321-331.

Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs. / Shimizu, Tadayori; Iwamoto, Yoshihisa; Yanagihara, Yasutake; Ryoyama, Kazuo; Suhara, Yoshitomo; Ikeda, Kiyoshi; Achiwa, Kazuo.

In: Immunobiology, Vol. 196, No. 4, 1996, p. 321-331.

Research output: Contribution to journalArticle

Shimizu, T, Iwamoto, Y, Yanagihara, Y, Ryoyama, K, Suhara, Y, Ikeda, K & Achiwa, K 1996, 'Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs', Immunobiology, vol. 196, no. 4, pp. 321-331.
Shimizu, Tadayori ; Iwamoto, Yoshihisa ; Yanagihara, Yasutake ; Ryoyama, Kazuo ; Suhara, Yoshitomo ; Ikeda, Kiyoshi ; Achiwa, Kazuo. / Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs. In: Immunobiology. 1996 ; Vol. 196, No. 4. pp. 321-331.
@article{69515d045311473bb4af6b4e9cb7a975,
title = "Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs",
abstract = "The mitogenicity, lethal toxicity, induction of tumor necrosis factor (TNF), production of nitric oxide (NO) and antitumor activity against Meth A fibrosarcoma by chemically synthesized N-acylated asparagine-linked (A-701, A-702 and A-703) or N-acylated serine-linked (A-607) nonphosphorylated acylglucosamine and 4-O-phosphorylated acylglucosamine (A-103) derived lipid A analogs were determined. Compound A-607 (with tetradecanoyl and (R)-3-tetradecanoyloxyterradecanoyl at the C-2 and C-3 positions) induced a significant incorporation of 3H-thymidine into splenocytes of C3H/He mice at concentrations ranging from 3.13 to 50 μM, but the mitogenic activity of A-701 (2-N-acetylglucosamine), A-702 (tetradecanoyl at the C-2), and A-703 (with (R)-tetradecanoyloxytetradecanoyl and tetradecanoyl at the C-2 and C-3) was very weak. The lethality of A-703 and A-103 (with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 and C-3) was weaker than that of A-607 at doses of 300 and 750 nmol/kg in C57BL/6 mice loaded with D-galactosamine. Peritoneal macrophages, stimulated with A-701-A-703, caused production of TNF which induce L929 cell lysis in vitro, and A-703 showed a high production of TNF. The compounds, except for A-607, exhibited little NO production by macrophages, but did induce the NO production in the presence of interferon gamma. Induction of TNF and NO inducible activity by A-703 was lower than that of A-607. A-703, A-607 and A-103 showed antitumor activity against Meth A fibrosarcoma in BALB/c mice. When A-703 or A-103 with muramyl dipeptide was administered, A-703 failed to show combined effects, but A-103 did. We concluded from these findings that the biological potency of asparagine compounds appears to be placed between serine- and amino-free compounds.",
author = "Tadayori Shimizu and Yoshihisa Iwamoto and Yasutake Yanagihara and Kazuo Ryoyama and Yoshitomo Suhara and Kiyoshi Ikeda and Kazuo Achiwa",
year = "1996",
language = "English",
volume = "196",
pages = "321--331",
journal = "Immunobiology",
issn = "0171-2985",
publisher = "Urban und Fischer Verlag GmbH und Co. KG",
number = "4",

}

TY - JOUR

T1 - Comparison of the biological activity of synthetic N-acylated asparagine or serine linked monosaccharide lipid A analogs

AU - Shimizu, Tadayori

AU - Iwamoto, Yoshihisa

AU - Yanagihara, Yasutake

AU - Ryoyama, Kazuo

AU - Suhara, Yoshitomo

AU - Ikeda, Kiyoshi

AU - Achiwa, Kazuo

PY - 1996

Y1 - 1996

N2 - The mitogenicity, lethal toxicity, induction of tumor necrosis factor (TNF), production of nitric oxide (NO) and antitumor activity against Meth A fibrosarcoma by chemically synthesized N-acylated asparagine-linked (A-701, A-702 and A-703) or N-acylated serine-linked (A-607) nonphosphorylated acylglucosamine and 4-O-phosphorylated acylglucosamine (A-103) derived lipid A analogs were determined. Compound A-607 (with tetradecanoyl and (R)-3-tetradecanoyloxyterradecanoyl at the C-2 and C-3 positions) induced a significant incorporation of 3H-thymidine into splenocytes of C3H/He mice at concentrations ranging from 3.13 to 50 μM, but the mitogenic activity of A-701 (2-N-acetylglucosamine), A-702 (tetradecanoyl at the C-2), and A-703 (with (R)-tetradecanoyloxytetradecanoyl and tetradecanoyl at the C-2 and C-3) was very weak. The lethality of A-703 and A-103 (with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 and C-3) was weaker than that of A-607 at doses of 300 and 750 nmol/kg in C57BL/6 mice loaded with D-galactosamine. Peritoneal macrophages, stimulated with A-701-A-703, caused production of TNF which induce L929 cell lysis in vitro, and A-703 showed a high production of TNF. The compounds, except for A-607, exhibited little NO production by macrophages, but did induce the NO production in the presence of interferon gamma. Induction of TNF and NO inducible activity by A-703 was lower than that of A-607. A-703, A-607 and A-103 showed antitumor activity against Meth A fibrosarcoma in BALB/c mice. When A-703 or A-103 with muramyl dipeptide was administered, A-703 failed to show combined effects, but A-103 did. We concluded from these findings that the biological potency of asparagine compounds appears to be placed between serine- and amino-free compounds.

AB - The mitogenicity, lethal toxicity, induction of tumor necrosis factor (TNF), production of nitric oxide (NO) and antitumor activity against Meth A fibrosarcoma by chemically synthesized N-acylated asparagine-linked (A-701, A-702 and A-703) or N-acylated serine-linked (A-607) nonphosphorylated acylglucosamine and 4-O-phosphorylated acylglucosamine (A-103) derived lipid A analogs were determined. Compound A-607 (with tetradecanoyl and (R)-3-tetradecanoyloxyterradecanoyl at the C-2 and C-3 positions) induced a significant incorporation of 3H-thymidine into splenocytes of C3H/He mice at concentrations ranging from 3.13 to 50 μM, but the mitogenic activity of A-701 (2-N-acetylglucosamine), A-702 (tetradecanoyl at the C-2), and A-703 (with (R)-tetradecanoyloxytetradecanoyl and tetradecanoyl at the C-2 and C-3) was very weak. The lethality of A-703 and A-103 (with (R)-3-tetradecanoyloxytetradecanoyl at the C-2 and C-3) was weaker than that of A-607 at doses of 300 and 750 nmol/kg in C57BL/6 mice loaded with D-galactosamine. Peritoneal macrophages, stimulated with A-701-A-703, caused production of TNF which induce L929 cell lysis in vitro, and A-703 showed a high production of TNF. The compounds, except for A-607, exhibited little NO production by macrophages, but did induce the NO production in the presence of interferon gamma. Induction of TNF and NO inducible activity by A-703 was lower than that of A-607. A-703, A-607 and A-103 showed antitumor activity against Meth A fibrosarcoma in BALB/c mice. When A-703 or A-103 with muramyl dipeptide was administered, A-703 failed to show combined effects, but A-103 did. We concluded from these findings that the biological potency of asparagine compounds appears to be placed between serine- and amino-free compounds.

UR - http://www.scopus.com/inward/record.url?scp=0030498663&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030498663&partnerID=8YFLogxK

M3 - Article

VL - 196

SP - 321

EP - 331

JO - Immunobiology

JF - Immunobiology

SN - 0171-2985

IS - 4

ER -