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Amino Acids

, Volume 50, Issue 12, pp 1697–1705 | Cite as

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

  • Vera A. Alferova
  • Maxim V. Shuvalov
  • Taisiya A. Suchkova
  • Gleb V. Proskurin
  • Ilya O. Aparin
  • Eugene A. Rogozhin
  • Roman A. Novikov
  • Pavel N. Solyev
  • Alexey A. Chistov
  • Alexey V. Ustinov
  • Anton P. Tyurin
  • Vladimir A. KorshunEmail author
Original Article
  • 266 Downloads

Abstract

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.

Keywords

Peptide antibiotics Amino acids 4-Chloro-l-kynurenine Fluorescence FRET 

Abbreviations

AcOH

Acetic acid

BODIPY FL

3-(4,4-Difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-yl)propanoic acid

DIPEA

N,N-Diisopropylethylamine

DMSO

Dimethyl sulfoxide

ESI Q-TOF

Electrospray ionization, quadrupole time-of-flight

EtOH

Ethanol

FDAA

Nα-(2,4-Dinitro-5-fluorophenyl)-l-alaninamide

FRET

Förster (fluorescence) resonance energy transfer

HPLC

High-performance liquid chromatography

HRMS

High-resolution mass spectrometry

ICT

Intramolecular charge transfer

Kyn

Kynurenine

LC–MS

Liquid chromatography/mass spectrometry

MeCN

Acetonitrile

MeOH

Methanol

NHS

N-Hydroxysuccinimide

NMDA

N-Methyl-d-aspartate

NMR

Nuclear magnetic resonance

PEPe

3-Phenylethynylperylene fluorophore (4-(perylen-3-ylethynyl)benzoic acid)

PET

Photoinduced electron transfer

Pfp

Pentafluorophenyl

TLC

Thin layer chromatography

Notes

Acknowledgements

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

726_2018_2642_MOESM1_ESM.pdf (977 kb)
Supplementary material 1 (PDF 977 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Gause Institute of New AntibioticsMoscowRussia
  2. 2.Department of ChemistryLomonosov Moscow State UniversityMoscowRussia
  3. 3.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryMoscowRussia
  4. 4.Engelhardt Institute of Molecular BiologyMoscowRussia
  5. 5.Orekhovich Research Institute of Biomedical ChemistryMoscowRussia

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