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.
Ingibirovanie post-skvalenovykh étapov biosinteza kholesterina predstavliaet soboĭ al'ternativu klassicheskoĭ statinovoĭ terapii. V kachestve odnoĭ iz vozmozhnykh molekuliarnykh misheneĭ rassmatrivaetsia steroid 14a-demetilaza (CYP51). V predstavlennoĭ rabote kombinatsieĭ metodov poverkhnostnogo plazmonnogo rezonansa i spektral'nogo titrovaniia byl osushchestvlen skrining potentsial'nykh ligandov CYP51 cheloveka s ispol'zovaniem serii prirodnykh soedineniĭ, soderzhashchikh steroid-podobnyĭ strukturnyĭ élement. Iz proanalizirovannoĭ vyborki 4 soedineniia (kapsikozin, betulafolientriol, goloturin A, teasaponin) kharakterizovalis' vysokoĭ affinnost'iu k aktivnomu tsentru CYP51A1. Poluchennye dannye rasshiriaiut spektr soedineniĭ, kotorye mogut byt' ispol'zovany v kachestve spetsificheskikh ingibitorov CYP51A1.
Keywords: CYP51; cytochrome P450; optical biosensor; spectral titration; surface plasmon resonance; triterpenes.