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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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Photoaffinity labeling (PAL) has become a popular tool in proteomics and drug discovery. PAL probes act via UV triggered free radicals generation followed by covalent bonding with a target molecule. Benzophenone (BP) derivatives are among such probes structures2. Often PAL probes include a reporter tag allowing better detection of labeled molecules, e.g. using fluorescence. Today borondipyrromethenes (BODIPYs) have become widely used as fluorophores due to their photostability and quantum yields. Both BODIPY and phenyl groups have planar cyclic conjugated structure, so BODIPY phenylketones (BPKs) can be considered as potential fluorescent analogs of BPbased PAL probes. However, there is only one research where BPK photoactivity has been mentioned3. Thus, we have synthesized a "minimalistic" BPK by acylation of 8methylBODIPY. Such acylation of a BODIPY been constructed on unsubstituted pyrroles hasn’t been described yet. The structure is characterized by NMR, ESIMS, UVvis spectrometry and fluorimetry. From quantummechanical calculations (PBE, madef2SVP)the HOMO/LUMO gap for 1 (1.78 eV) is smaller than for BP (2.88 eV) assuming that photoactivation of 1 can be achieved by less energetic light than BP. The compound was found to give an adduct with cytochrome P450 CYP7B1 after 365 nmUV exposition according to monitoring of the fluorescent band with the parent protein mobility on SDSPAGE. Molecular docking demonstrated affine binding of 1 with a set of human P450s (free binding energies up to 15,1 kcal/mol). Compound 1 is a potentially new photoactive fluorescent ligand. Thus, 1 and other BPKs can be developed as facile and powerful proteomic tools to reveal new structurefunction features of biomolecules. Grants BRFFI X19PM062 / X19PM0621 – RFFI 195404009 Bel_mol_a.