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Amino Acids

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Synthesis, characterization and anticonvulsant activity of new azobenzene-containing VV-hemorphin-5 bio photoswitch

  • Petar T. Todorov
  • Petia N. Peneva
  • Stela I. Georgieva
  • Jana Tchekalarova
  • Victoria Vitkova
  • Krassimira Antonova
  • Anton Georgiev
Original Article
  • 41 Downloads

Abstract

A novel analog of VV-hemorphin-5 containing azobenzene moiety has been synthesized and investigated for anticonvulsant activity in relation to its E → Z photophysical properties activated by long wavelength light at 365 nm. The synthesis was achieved by a modified SPPS by Fmoc-dimerization strategy. The electrochemical behavior before and after UV illumination was investigated using different voltammetric modes. The number of electrons transferred, heterogenic rate constant and diffusion coefficient for E- and Z-isomers were also evaluated. Revealing the governing principles involved in signaling and nerve pulse propagation requires the detailed characterization of the electrical properties of cell membranes. For probing the effect of synthesized azo-peptide on the membrane electrical properties, we measured the specific capacitance of lipid bilayers, representing a basic physical model of biomembranes with their simple reproducibility in laboratory conditions at controlled membrane composition and physicochemical parameters of the surrounding aqueous medium. Our results have shown reduced membrane capacitance in the presence of the azo-peptide, thus providing evidences for possible alterations in the dielectric permittivity of the bilayer. The (Val-Val-Tyr-Pro-Trp-Thr-Gln)2Azo peptide was explored also in vivo for preliminary anticonvulsant activity by using the 6-Hz seizure test and pentylenetetrazol (PTZ) seizure test in mice. The Z-isomer has exhibited higher potency compared to E-isomer most pronouncedly in the 6 Hz test for psychomotor seizures where the compound had activity at all three tested doses. It was found that the Z-isomer decrease the latency for onset of clonic seizures induced by PTZ. These results demonstrate that the Z-isomer deserves further evaluation in other screening tests for anticonvulsant activity.

Keywords

Azobenzene-peptides Hemorphins SPPS Anticonvulsant activity Trans–cis photoisomerization Bio photoswitches Electrochemistry 

Notes

Acknowledgements

This work was financially supported by the Bulgarian National Scientific Fund project ДH 18/5 of the Ministry of Education and Science, Bulgaria.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical statement

All procedures were performed in agreement with the European Communities Council Directive 2010/63/EU. The experimental design was approved by the Institutional Ethics Committee. There were no human participants.

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Organic ChemistryUniversity of Chemical Technology and MetallurgySofiaBulgaria
  2. 2.Department of Analytical ChemistryUniversity of Chemical Technology and MetallurgySofiaBulgaria
  3. 3.Institute of NeurobiologyBulgarian Academy of SciencesSofiaBulgaria
  4. 4.Institute of Solid State PhysicsBulgarian Academy of SciencesSofiaBulgaria
  5. 5.Department of Optical Metrology and Holography, Institute of Optical Materials and TechnologiesBulgarian Academy of ScienceSofiaBulgaria

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