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4-Chloro-L-kynurenine as fluorescent amino acid in natural peptides

Alferova, Vera A., Shuvalov, Maxim V., Suchkova, Taisiya A., Proskurin, Gleb V., Aparin, Ilya O., Rogozhin, Eugene A., Novikov, Roman A., Solyev, Pavel N., Chistov, Alexey A., Ustinov, Alexey V., Tyurin, Anton P., Korshun, Vladimir A.
Amino acids 2018 v.50 no.12 pp. 1697-1705
acid hydrolysis, amino acids, antibiotics, antidepressants, energy transfer, fluorescence, fluorescent substances, lipopeptides, mechanism of action, solvents, spectral analysis
4-Chloro-L-kynurenine (3-(4-chloroanthraniloyl)-L-alanine, L-4-ClKyn), an amino acid known as a prospective antidepressant, was recently for the first time found in nature in the lipopeptide antibiotic taromycin. Here, we report another instance of its identification in a natural product: 4-chloro-L-kynurenine was isolated from acidic hydrolysis of a new complex peptide antibiotic INA-5812. L-4-ClKyn is a fluorescent compound responsible for the fluorescence of the above antibiotic. Whereas fluorescence of 4-chlorokynurenine was not reported before, we synthesized the racemic compound and studied its emission in various solvents. Next, we prepared conjugates of DL-4-ClKyn with two suitable energy acceptors, BODIPY FL and 3-(phenylethynyl)perylene (PEPe), and studied fluorescence of the derivatives. 4-Chloro-DL-kynurenine emission is not detected in both conjugates, thus evidencing effective energy transfer. However, BODIPY FL emission in the conjugate is substantially reduced, probably due to collisional or photoinduced charge-transfer-mediated quenching. The intrinsic fluorescence of L-4-ClKyn amino acid in antibiotics paves the way for spectral studies of their mode of action.