1. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences 2. Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus 3. National Research Center for Pediatric Oncology, Hematology and Immunology 4. Elyakov Pacific Institute of Bioorganic Chemistry FEB RAS
Abstract: The cholesterol biosynthesis regulation is the important part of the hypercholesterolemia diseases therapy. The inhibition of the post-squalene cholesterol biosynthesis steps provide the alternative to classic statin therapy. Sterol-14a-demethylase (CYP51) is one of the hypothetical targets for it. In this work the screening of the ability to interact with human CYP51 (CYP51A1) for the nature low-weight compounds with steroid-like scaffold were performed by integration of the surface plasmon resonance biosensor and spectral titration methods. The results of the selection were 4 compounds (betulafolientriol, holothurin A, teasaponin, capsicoside A) witch had high affinity to the CYP51A1 active site. These data extend the range of compounds which may be used as specific inhibitors of CYP51 and give the permission to suggest the dynamic of the enzyme.
Reference: Kaluzhskiy L.A., Gnedenko O.V., Gilep A.A., Strushkevich N.V., Shkel T.V., Chernovetsky M.A., Ivanov A.S., Lisitsa A.V., Usanov S.A., Stonik V.A., Archakov A.I., The screening of the inhibitors of the human cytochrome P450(51) (CYP51A1): the plant and animal structural lanosterol's analogs, Biomeditsinskaya khimiya, 2014, vol: