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