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Discovery of (S)-3′-hydroxyblebbistatin and (S)-3′-aminoblebbistatin : polar myosin II inhibitors with superior research tool properties

Sigrid Verhasselt UGent, Bart Roman UGent, Olivier De Wever UGent, Kristof Van Hecke UGent, Rik Van Deun UGent, Marc Bracke UGent and Christian Stevens UGent (2017) ORGANIC & BIOMOLECULAR CHEMISTRY. 15(9). p.2104-2118
abstract
In search of myosin II inhibitors with superior research tool properties, a chemical optimization campaign of the blebbistatin scaffold was conducted in this paper. (S)-Blebbistatin is the best known small-molecule inhibitor of myosin II ATPase activity. Unfortunately, as a research tool this compound has several deficiencies: it is photolabile and (photo) toxic, has low water solubility, and its (fluorescent) precipitates interfere in (fluorescence) readouts. In view of obtaining tool compounds with improved properties, both enantiomers of a series of D-ring modified polar analogs were prepared. We identified (S)-3'-hydroxyblebbistatin (S)-2 and (S)-3'-aminoblebbistatin (S)-3 as two myosin II inhibitors with a 30-fold higher water solubility than (S)-blebbistatin. These molecules furthermore do not cause interference in (fluorescence) readouts. (S)-2 and (S)-3 thus are superior alternatives to (S)-blebbistatin as research tools to study myosin II.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CANCER-CELLS, BLUE-LIGHT, BLEBBISTATIN, MECHANISM, MIGRATION, INVASION, HEARTS, MUSCLE
journal title
ORGANIC & BIOMOLECULAR CHEMISTRY
Org. Biomol. Chem.
volume
15
issue
9
pages
2104 - 2118
Web of Science type
Article
Web of Science id
000395928400020
ISSN
1477-0520
1477-0539
DOI
10.1039/c7ob00006e
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8514040
handle
http://hdl.handle.net/1854/LU-8514040
date created
2017-03-11 10:17:09
date last changed
2018-03-09 23:30:09
@article{8514040,
  abstract     = {In search of myosin II inhibitors with superior research tool properties, a chemical optimization campaign of the blebbistatin scaffold was conducted in this paper. (S)-Blebbistatin is the best known small-molecule inhibitor of myosin II ATPase activity. Unfortunately, as a research tool this compound has several deficiencies: it is photolabile and (photo) toxic, has low water solubility, and its (fluorescent) precipitates interfere in (fluorescence) readouts. In view of obtaining tool compounds with improved properties, both enantiomers of a series of D-ring modified polar analogs were prepared. We identified (S)-3'-hydroxyblebbistatin (S)-2 and (S)-3'-aminoblebbistatin (S)-3 as two myosin II inhibitors with a 30-fold higher water solubility than (S)-blebbistatin. These molecules furthermore do not cause interference in (fluorescence) readouts. (S)-2 and (S)-3 thus are superior alternatives to (S)-blebbistatin as research tools to study myosin II.},
  author       = {Verhasselt, Sigrid and Roman, Bart and De Wever, Olivier and Van Hecke, Kristof and Van Deun, Rik and Bracke, Marc and Stevens, Christian},
  issn         = {1477-0520},
  journal      = {ORGANIC \& BIOMOLECULAR CHEMISTRY},
  keyword      = {CANCER-CELLS,BLUE-LIGHT,BLEBBISTATIN,MECHANISM,MIGRATION,INVASION,HEARTS,MUSCLE},
  language     = {eng},
  number       = {9},
  pages        = {2104--2118},
  title        = {Discovery of (S)-3{\textquotesingle}-hydroxyblebbistatin and (S)-3{\textquotesingle}-aminoblebbistatin : polar myosin II inhibitors with superior research tool properties},
  url          = {http://dx.doi.org/10.1039/c7ob00006e},
  volume       = {15},
  year         = {2017},
}

Chicago
Verhasselt, Sigrid, Bart Roman, Olivier De Wever, Kristof Van Hecke, Rik Van Deun, Marc Bracke, and Christian Stevens. 2017. “Discovery of (S)-3′-hydroxyblebbistatin and (S)-3′-aminoblebbistatin : Polar Myosin II Inhibitors with Superior Research Tool Properties.” Organic & Biomolecular Chemistry 15 (9): 2104–2118.
APA
Verhasselt, S., Roman, B., De Wever, O., Van Hecke, K., Van Deun, R., Bracke, M., & Stevens, C. (2017). Discovery of (S)-3′-hydroxyblebbistatin and (S)-3′-aminoblebbistatin : polar myosin II inhibitors with superior research tool properties. ORGANIC & BIOMOLECULAR CHEMISTRY, 15(9), 2104–2118.
Vancouver
1.
Verhasselt S, Roman B, De Wever O, Van Hecke K, Van Deun R, Bracke M, et al. Discovery of (S)-3′-hydroxyblebbistatin and (S)-3′-aminoblebbistatin : polar myosin II inhibitors with superior research tool properties. ORGANIC & BIOMOLECULAR CHEMISTRY. 2017;15(9):2104–18.
MLA
Verhasselt, Sigrid, Bart Roman, Olivier De Wever, et al. “Discovery of (S)-3′-hydroxyblebbistatin and (S)-3′-aminoblebbistatin : Polar Myosin II Inhibitors with Superior Research Tool Properties.” ORGANIC & BIOMOLECULAR CHEMISTRY 15.9 (2017): 2104–2118. Print.