03054nab a2200373 i 4500 publ37607 20250903081132.0 250903s2025 hu o 000 eng d 1661-6596 10.3390/ijms26157075 doi 36263554 mtmt SZTE Publicatio Repozitórium hun eng Hlogyik Tamás The Red Shift in Estrogen Research [elektronikus dokumentum] : An Estrogen-Receptor Targeted aza-BODIPY–Estradiol Fluorescent Conjugate / Hlogyik Tamás 2025 18 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 26 No. 15 Estradiol (E2) plays an important role in cell proliferation and certain brain functions. To reveal its mechanism of action, its detectability is essential. Only a few fluorescent-labeled hormonally active E2s exist in the literature, and their mechanism of action usually remains unclear. It would be of particular interest to develop novel labeled estradiol derivatives with retained biological activity and improved optical properties. Due to their superior optical characteristics, aza-BODIPY dyes are frequently used labeling agents in biomedical applications. E2 was labeled with the aza-BODIPY dye at its phenolic hydroxy function via an alkyl linker and a triazole coupling moiety. The estrogenic activity of the newly synthesized fluorescent conjugate was evaluated via transcriptional luciferase assay. Docking calculations were performed for the classical and alternative binding sites (CBS and ABS) of human estrogen receptor α. The terminal alkyne function was introduced into the tetraphenyl aza-BODIPY core via selective formylation, oxidation, and subsequent amidation with propargyl amine. The conjugation was achieved via Cu(I)-catalyzed azide–alkyne click reaction of the aza-BODIPY-alkyne with the 3-O-(4-azidobut-1-yl) derivative of E2. The labeled estrogen induced a dose-dependent transcriptional activity of human estrogen receptor α with a submicromolar EC50 value. Docking calculations revealed that the steroid part has a perfect overlap with E2 in ABS. In CBS, however, a head-tail binding deviation was observed. A facile, fluorescent labeling methodology has been elaborated for the development of a novel red-emitting E2 conjugate with substantial estrogenic activity. Docking experiments uncovered the binding mode of the conjugate in both ABS and CBS. Általános orvostudomány Bózsity-Faragó Noémi aut Börzsei Rita aut Kovács Benjamin aut Labos Péter aut Hetényi Csaba aut Csontné Kiricsi Mónika aut Huliák Ildikó aut Kele Zoltán aut Poór Miklós aut Erostyák János aut Hunyadi Attila aut Zupkó István aut Mernyák Erzsébet aut http://publicatio.bibl.u-szeged.hu/37607/1/ijms-26-07075.pdf Dokumentum-elérés