Discovery and validation of 2-styryl substituted benzoxazin-4-ones as a novel scaffold for rhomboid protease inhibitors
Graphical abstract
Section snippets
Results and discussion
Rhomboids are intramembrane serine proteases present in prokaryotic, archaeal and eukaryotic organisms.1 In 2001, the first rhomboid was discovered in Drosophila and shown to perform a critical proteolysis step in EGF-receptor signaling.2, 3 Since then, rhomboids have been implicated in a wide range of biological processes including bacterial quorum sensing4, mitochondrial dynamics and integrity5, 6, and protein quality control.7 In addition, rhomboids have been identified as putative drug
Acknowledgements
We thank Professors Matthew Freeman (University of Oxford) and Ya Ha (Yale School of Medicine) for bacterial expression constructs. P.G. was supported by a scholarship of the iGRASPseed graduate school of the Heinrich-Heine-University Duesseldorf. K.S. was a recipient of the Purkyne Fellowship of the Academy of Sciences of the Czech Republic and also acknowledges support from the Ministry of Education, Youth and Sports of the Czech Republic (projects no. LK11206 and LO1302), Marie Curie Career
Conflicts of interest
None.
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