Small-molecule-induced clustering of heparan sulfate promotes cell adhesion

Naohiro Takemoto; Tetsuya Suehara; Heidie L. Frisco; Shin Ichi Sato; Takuhito Sezaki; Kosuke Kusamori; Yoshinori Kawazoe; Sun Min Park; Sayumi Yamazoe; Yoshiyuki Mizuhata; Rintaro Inoue; Gavin J. Miller; Steen U. Hansen; Gordon C. Jayson; John M. Gardiner; Toshiji Kanaya; Norihiro Tokitoh; Kazumitsu Ueda; Yoshinobu Takakura; Noriyuki Kioka; Makiya Nishikawa; Motonari Uesugi

doi:10.1021/ja4018682

Small-molecule-induced clustering of heparan sulfate promotes cell adhesion

Naohiro Takemoto, Tetsuya Suehara, Heidie L. Frisco, Shin Ichi Sato, Takuhito Sezaki, Kosuke Kusamori, Yoshinori Kawazoe, Sun Min Park, Sayumi Yamazoe, Yoshiyuki Mizuhata, Rintaro Inoue, Gavin J. Miller, Steen U. Hansen, Gordon C. Jayson, John M. Gardiner, Toshiji Kanaya, Norihiro Tokitoh, Kazumitsu Ueda, Yoshinobu Takakura, Noriyuki KiokaMakiya Nishikawa, Motonari Uesugi

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Abstract

Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy. © 2013 American Chemical Society.

Original language	English
Pages (from-to)	11032-11039
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	135
Issue number	30
DOIs	https://doi.org/10.1021/ja4018682
Publication status	Published - 31 Jul 2013

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10.1021/ja4018682

CCDC 850155: Experimental Crystal Structure Determination
Takemoto, N. (Contributor), Suehara, T. (Contributor), Frisco, H. L. (Contributor), Sato, S. I. (Contributor), Sezaki, T. (Contributor), Kusamori, K. (Contributor), Kawazoe, Y. (Contributor), Park, S. M. (Contributor), Yamazoe, S. (Contributor), Mizuhata, Y. (Contributor), Inoue, R. (Contributor), Miller, G. (Contributor), Hansen, S. U. (Contributor), Jayson, G. (Contributor), Gardiner, J. (Contributor), Kanaya, T. (Contributor), Tokitoh, N. (Contributor), Ueda, K. (Contributor), Takakura, Y. (Contributor), Kioka, N. (Contributor), Nishikawa, M. (Contributor) & Uesugi, M. (Contributor), Cambridge Crystallographic Data Centre, 1 Jan 2014
DOI: 10.5517/ccxjncf, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccxjncf&sid=DataCite
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Takemoto, N., Suehara, T., Frisco, H. L., Sato, S. I., Sezaki, T., Kusamori, K., Kawazoe, Y., Park, S. M., Yamazoe, S., Mizuhata, Y., Inoue, R., Miller, G. J., Hansen, S. U., Jayson, G. C., Gardiner, J. M., Kanaya, T., Tokitoh, N., Ueda, K., Takakura, Y., ... Uesugi, M. (2013). Small-molecule-induced clustering of heparan sulfate promotes cell adhesion. Journal of the American Chemical Society, 135(30), 11032-11039. https://doi.org/10.1021/ja4018682

@article{55667f9024d44c85af8c4c9ea06efb5b,

title = "Small-molecule-induced clustering of heparan sulfate promotes cell adhesion",

abstract = "Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy. {\textcopyright} 2013 American Chemical Society.",

author = "Naohiro Takemoto and Tetsuya Suehara and Frisco, {Heidie L.} and Sato, {Shin Ichi} and Takuhito Sezaki and Kosuke Kusamori and Yoshinori Kawazoe and Park, {Sun Min} and Sayumi Yamazoe and Yoshiyuki Mizuhata and Rintaro Inoue and Miller, {Gavin J.} and Hansen, {Steen U.} and Jayson, {Gordon C.} and Gardiner, {John M.} and Toshiji Kanaya and Norihiro Tokitoh and Kazumitsu Ueda and Yoshinobu Takakura and Noriyuki Kioka and Makiya Nishikawa and Motonari Uesugi",

year = "2013",

month = jul,

day = "31",

doi = "10.1021/ja4018682",

language = "English",

volume = "135",

pages = "11032--11039",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "30",

}

Takemoto, N, Suehara, T, Frisco, HL, Sato, SI, Sezaki, T, Kusamori, K, Kawazoe, Y, Park, SM, Yamazoe, S, Mizuhata, Y, Inoue, R, Miller, GJ, Hansen, SU, Jayson, GC , Gardiner, JM, Kanaya, T, Tokitoh, N, Ueda, K, Takakura, Y, Kioka, N, Nishikawa, M & Uesugi, M 2013, 'Small-molecule-induced clustering of heparan sulfate promotes cell adhesion', Journal of the American Chemical Society, vol. 135, no. 30, pp. 11032-11039. https://doi.org/10.1021/ja4018682

TY - JOUR

T1 - Small-molecule-induced clustering of heparan sulfate promotes cell adhesion

AU - Takemoto, Naohiro

AU - Suehara, Tetsuya

AU - Frisco, Heidie L.

AU - Sato, Shin Ichi

AU - Sezaki, Takuhito

AU - Kusamori, Kosuke

AU - Kawazoe, Yoshinori

AU - Park, Sun Min

AU - Yamazoe, Sayumi

AU - Mizuhata, Yoshiyuki

AU - Inoue, Rintaro

AU - Miller, Gavin J.

AU - Hansen, Steen U.

AU - Jayson, Gordon C.

AU - Gardiner, John M.

AU - Kanaya, Toshiji

AU - Tokitoh, Norihiro

AU - Ueda, Kazumitsu

AU - Takakura, Yoshinobu

AU - Kioka, Noriyuki

AU - Nishikawa, Makiya

AU - Uesugi, Motonari

PY - 2013/7/31

Y1 - 2013/7/31

N2 - Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy. © 2013 American Chemical Society.

AB - Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy. © 2013 American Chemical Society.

U2 - 10.1021/ja4018682

DO - 10.1021/ja4018682

M3 - Article

C2 - 23822587

SN - 0002-7863

VL - 135

SP - 11032

EP - 11039

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 30

ER -

Small-molecule-induced clustering of heparan sulfate promotes cell adhesion

Abstract

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Datasets

CCDC 850155: Experimental Crystal Structure Determination

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