Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency
- Author
- Bart Roman (UGent) , Sigrid Verhasselt (UGent) , Christophe Mangodt (UGent) , Olivier De Wever (UGent) and Christian Stevens (UGent)
- Organization
- Abstract
- (S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy.
- Keywords
- Blebbistatin, Inhibitor, Myosin, ATPase, C-ring, MODIFIED (S)-BLEBBISTATIN ANALOGS, TOOL PROPERTIES, INSIGHTS, ESTERS
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8565153
- MLA
- Roman, Bart, et al. “Synthesis of C-Ring-Modified Blebbistatin Derivatives and Evaluation of Their Myosin II ATPase Inhibitory Potency.” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 28, no. 13, 2018, pp. 2261–64, doi:10.1016/j.bmcl.2018.05.041.
- APA
- Roman, B., Verhasselt, S., Mangodt, C., De Wever, O., & Stevens, C. (2018). Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 28(13), 2261–2264. https://doi.org/10.1016/j.bmcl.2018.05.041
- Chicago author-date
- Roman, Bart, Sigrid Verhasselt, Christophe Mangodt, Olivier De Wever, and Christian Stevens. 2018. “Synthesis of C-Ring-Modified Blebbistatin Derivatives and Evaluation of Their Myosin II ATPase Inhibitory Potency.” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 28 (13): 2261–64. https://doi.org/10.1016/j.bmcl.2018.05.041.
- Chicago author-date (all authors)
- Roman, Bart, Sigrid Verhasselt, Christophe Mangodt, Olivier De Wever, and Christian Stevens. 2018. “Synthesis of C-Ring-Modified Blebbistatin Derivatives and Evaluation of Their Myosin II ATPase Inhibitory Potency.” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 28 (13): 2261–2264. doi:10.1016/j.bmcl.2018.05.041.
- Vancouver
- 1.Roman B, Verhasselt S, Mangodt C, De Wever O, Stevens C. Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. 2018;28(13):2261–4.
- IEEE
- [1]B. Roman, S. Verhasselt, C. Mangodt, O. De Wever, and C. Stevens, “Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency,” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 28, no. 13, pp. 2261–2264, 2018.
@article{8565153,
abstract = {{(S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy.}},
author = {{Roman, Bart and Verhasselt, Sigrid and Mangodt, Christophe and De Wever, Olivier and Stevens, Christian}},
issn = {{0960-894X}},
journal = {{BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}},
keywords = {{Blebbistatin,Inhibitor,Myosin,ATPase,C-ring,MODIFIED (S)-BLEBBISTATIN ANALOGS,TOOL PROPERTIES,INSIGHTS,ESTERS}},
language = {{eng}},
number = {{13}},
pages = {{2261--2264}},
title = {{Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency}},
url = {{http://doi.org/10.1016/j.bmcl.2018.05.041}},
volume = {{28}},
year = {{2018}},
}
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