Small-Molecule-Induced Clustering of Heparan Sulfate Promotes Cell Adhesion
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- 作者：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
- 刊名：The Journal of the American Chemical Society
- 出版年：2013
- 出版时间：July 31, 2013
- 年：2013
- 卷：135
- 期：30
- 页码：11032-11039
- 全文大小：359K
- 年卷期：v.135,no.30(July 31, 2013)
- ISSN：1520-5126
文摘
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.