Para-nitroblebbistatin, the non-cytotoxic and photostable myosin II inhibitor

Miklós Képiró, Boglárka H. Várkuti, László Végner, Gergely Vörös, György Hegyi, Máté Varga, András Málnási-Csizmadia

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Blebbistatin, the best characterized myosin II-inhibitor, is commonly used to study the biological roles of various myosin II isoforms. Despite its popularity, the use of blebbistatin is greatly hindered by its blue-light sensitivity, resulting in phototoxicity and photoconversion of the molecule. Additionally, blebbistatin has serious cytotoxic side effects even in the absence of irradiation, which may easily lead to the misinterpretation of experimental results since the cytotoxicity-derived phenotype could be attributed to the inhibition of the myosin II function. Here we report the synthesis as well as the in vitro and in vivo characterization of a photostable, C15 nitro derivative of blebbistatin with unaffected myosin II inhibitory properties. Importantly, para-nitroblebbistatin is neither phototoxic nor cytotoxic, as shown by cellular and animal tests; therefore it can serve as an unrestricted and complete replacement of blebbistatin both in vitro and in vivo.

Original languageEnglish
Pages (from-to)8211-8215
Number of pages5
JournalAngewandte Chemie - International Edition
Volume53
Issue number31
DOIs
Publication statusPublished - Jul 28 2014

Keywords

  • asymmetric synthesis
  • cytotoxicity
  • enzymes
  • inhibitors
  • proteins

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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