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para ‐Nitroblebbistatin, the Non‐Cytotoxic and Photostable Myosin II Inhibitor
Author(s) -
Képiró Miklós,
Várkuti Boglárka H.,
Végner László,
Vörös Gergely,
Hegyi György,
Varga Máté,
MálnásiCsizmadia András
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201403540
Subject(s) - myosin , phototoxicity , in vivo , cytotoxic t cell , cytotoxicity , chemistry , in vitro , microbiology and biotechnology , biochemistry , biophysics , biology
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.