4-Chloro-l-kynurenine as fluorescent amino acid in natural peptides
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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.
KeywordsPeptide antibiotics Amino acids 4-Chloro-l-kynurenine Fluorescence FRET
- BODIPY FL
- ESI Q-TOF
Electrospray ionization, quadrupole time-of-flight
Förster (fluorescence) resonance energy transfer
High-performance liquid chromatography
High-resolution mass spectrometry
Intramolecular charge transfer
Liquid chromatography/mass spectrometry
Nuclear magnetic resonance
3-Phenylethynylperylene fluorophore (4-(perylen-3-ylethynyl)benzoic acid)
Photoinduced electron transfer
Thin layer chromatography
The research was supported in part by Russian Science Foundation (project No. 15-15-00053, synthesis and study of PEPe derivatives). HRMS and NMR studies were supported by the Program of fundamental research of the Russian Academy of Sciences (No. 01201363818). We thank Alexander Korolev for helpful advice at the initial stages of the research.
Compliance with ethical standards
Conflict of interest
The authors declare that they do not have any conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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