Functional 1,3a,6a-triazapentalene scaffold: Design of fluorescent probes for kinesin spindle protein (KSP)

Jun-Ichi Sawada; Ayumi Osawa; Tomoki Takeuchi; Masato Kaneda; Shinya Oishi; Nobutaka Fujii; Akira Asai; Keiji Tanino; Kosuke Namba

doi:10.1016/j.bmcl.2016.10.047

Functional 1,3a,6a-triazapentalene scaffold: Design of fluorescent probes for kinesin spindle protein (KSP)

Bioorg Med Chem Lett. 2016 Dec 1;26(23):5765-5769. doi: 10.1016/j.bmcl.2016.10.047. Epub 2016 Oct 15.

Authors

Jun-Ichi Sawada¹, Ayumi Osawa², Tomoki Takeuchi³, Masato Kaneda³, Shinya Oishi⁴, Nobutaka Fujii³, Akira Asai⁵, Keiji Tanino⁶, Kosuke Namba⁷

Affiliations

¹ Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan.
² Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
³ Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
⁴ Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: soishi@pharm.kyoto-u.ac.jp.
⁵ Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: aasai@u-shizuoka-ken.ac.jp.
⁶ Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.
⁷ Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770-8505, Japan; Department of Chemistry, Faculty of Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan.

PMID: 27793568
DOI: 10.1016/j.bmcl.2016.10.047

Abstract

1,3a,6a-Triazapentalene is a compact fluorescent chromophore. In this study, triazapentalene was used to modify a series of biphenyl-type inhibitors of kinesin spindle protein (KSP) to develop fluorescent probes for the intracellular visualization of this protein. Microscopic studies demonstrated that these novel triazapentalene-labeled compounds exhibited inhibitory activity towards KSP in cultured cells and provided important information concerning the intracellular distribution.

Keywords: KSP; Kinesin spindle protein; Probe; Triazapentalene.

MeSH terms

Biphenyl Compounds / chemistry
Biphenyl Compounds / pharmacology
Bridged Bicyclo Compounds, Heterocyclic / chemistry*
Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
Cell Proliferation / drug effects
Fluorescent Dyes / chemistry*
Fluorescent Dyes / pharmacology*
HeLa Cells
Humans
Kinesins / analysis*
Kinesins / antagonists & inhibitors*
Microscopy, Fluorescence

Substances

1,3a,6a-triazapentalene
Biphenyl Compounds
Bridged Bicyclo Compounds, Heterocyclic
Fluorescent Dyes
KIF11 protein, human
diphenyl
Kinesins