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Design, synthesis and in silico evaluation of a new molecular probe for covalent modification of human cytochromes P450 and STARD1 proteinтезисы доклада Электронная публикация Научная брошюра
- Авторы: Faletrov Y.V., Horetsky M.S., Frolova N.S., Rudaya E.V., Rubtsov M.A., Novikova L.A., Tugaeva K.V., Sluchanko N.N., Dichenko Y.V., Shkumatov V.M.
- Сборник: Тезисы докладов III Международной конференци "Свободные радикалы в химии и жизни/ Free radicals in chemistry and life", Пленарные выступления/Plenary reports, Минск, БГУ, 10-11 октября, 2019 г
- Тезисы
- Год издания: 2019
- Место издания: Минск, БГУ
- Первая страница: 6
- Аннотация: Free radicals in chemistry and life [Электронный ресурс] : тез. докл. III Междунар. конф., Минск,10–11 окт. 2019 г. / Белорус. гос. ун-т ; редкол.: О. И. Шадыро (отв. ред.) [и др.]. – Минск : БГУ, 2019. ISBN 978-985-566-814-6. Steroids play many roles essential for both normal and pathological states of human cells and body [1]. Thus, chemically-modified steroids have found good application as drugs or molecular probes for the process management or monitoring, respectively [2, 3]. We have synthesized a new steroidal diazirine, 17-(methyl(4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzyl)amino)-androst-5-en-3beta-ol (DAMDz1), using reductive amination followed by nucleophilic substitution. Data from ESI-MS (signal from [M+H]+ ion with m/z 502.4), HPLC-UV (single peak at 205 nm with RT 24.1 min; spectrum with maxima at 220 and 360 nm) and NMR confirm DAMDz1 structure. Free radical pho-tochemistry of diazirine means 365 nm UV irradiation-induced formation of highly reactive triplet carbene, which forms a covalent adduct with amino acid of a protein-of-interest or other biomolecule in the case of co-localization, re-sulting in photo-crosslinking. Autodock Vina reverse virtual screening allows us to find that DAMDz1 can be bound in the active sites of cytochromes P450 CYP11A1, CYP3A4 and transport protein STARD1 in a proved ligand-like manner with a good affinity (theoretical energy of binding within -13 – -11 kcal/mol). This work impacts on development of photo-affinity probes for var-ious steroid-binding proteins. This work was supported by the BRFFI (Х19РМ-062 and Х19РМ-062-1) – RFFI (19-54-04009 Бел_мол_а) joint grant.
- Добавил в систему: Новикова Людмила Александровна