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Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency

Bart Roman (UGent) , Sigrid Verhasselt (UGent) , Christophe Mangodt (UGent) , Olivier De Wever (UGent) and Christian Stevens (UGent)
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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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Chicago
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.
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.
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.
MLA
Roman, Bart, Sigrid Verhasselt, Christophe Mangodt, et al. “Synthesis of C-ring-modified Blebbistatin Derivatives and Evaluation of Their Myosin II ATPase Inhibitory Potency.” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 28.13 (2018): 2261–2264. Print.
@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://dx.doi.org/10.1016/j.bmcl.2018.05.041},
  volume       = {28},
  year         = {2018},
}

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