Discovery of the potential of cholesterol-lowering human CYP7 enzymes as biocatalysts for the production of C7 hydroxylated steroids.

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Tác giả: Jovana Ajduković, Tatsiana Cherkesova, Yaraslau Dzichenka, Ljubica Grbović, Suzana Jovanović-Šanta, Ivana Kuzminac, Andrea Nikolić, Aleksandar Oklješa, Ksenija Pavlović, Antos Sachanka, Marina Savić, Michail Shapira, Veronika Shchur, Sergey Usanov, Bojana Vasiljević, Aliaksei Yantsevich

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : Biophysical chemistry , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 91212

Steroidal C7 alcohols and their esters are perspective agents in drug discovery. In addition, hydroxylation at C7 position could allow further modification of steroidal moiety. Such transformation is performed easily by the enzymes. Human steroid 7α-hydroxylases CYP7A1 and CYP7B1 are key enzymes taking part in the biotransformation of cholestanes, androstanes, pregnanes. In the article, we are focusing on the results of in vitro screening of a library of modified steroids toward CYP7 enzymes. A couple of compounds were found to express the affinity for binding to the enzymes, comparable with corresponding values for CYP7 natural ligands. Among them are 17-substituted androstane derivatives with N-containing pyridine ring and enone derivative of lithocholic acid, which bound by human CYP7A1, and D-seco and C16 oxime androstanes, which were identified as novel CYP7B1 ligands. Screening results revealed that both enzymes bind with high affinity a well-known drug abiraterone: in the case of CYP7A1 substrate-like binding mode was detected, with the formation of monohydroxylated product, while in case of CYP7B1 inhibitor-like binding was observed. Since CYP7 enzymes convert some of the studied compounds into their 7-hydroxy derivatives, potential of these enzymes as perspective regio- and stereoselective biocatalysts for obtaining C7 hydroxylated steroids could be assumed.
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