Spectral and electrochemical solvatochromic investigations of newly synthesized peptide-based chemosensor bearing azobenzene side chain bio photoswitch

ABSTRACT In the present study, a novel analogue of azobenzene-containing hemorphin-4 has been synthesized and investigated for assessment of spectral, electrochemical, and biological effects. The synthesis was achieved by a modified solid-phase peptide synthesis (SPPS) by Fmoc-strategy. This compound represents a newly synthesized and unstudied peptide-based chemosensor bearing azobenzene side-chain with different spectral and electrochemical properties in the two trans-/cis-states depending on the solvent polarity. Their fluorescence intensity, as well as voltammetric behavior, was found to depend on both the polarity of the solvents and the type of isomers of the azopeptide compound. The influence of the metal ions such as Zn 2+ , Ni 2+ , and Cu 2+ on the fluorescence emission intensity of trans-forms in a water solution of the azopeptide has been also studied. Both isomer forms have shown significant pH dependence, as the fluorescence peak and intensity are significantly distinguished in acidic and neutral medium. The electrochemical behavior before and after 90 min UV illumination was investigated using a cyclic voltammetric mode at three-electrode system with HMDE electrode as the working electrode. The novel biopeptide Azo-Tyr-Pro-Trp-Thr-NH2 was explored in vivo for potential anticonvulsant activity by 6-Hz seizure test and maximal electroshock test (MES) in ICR mice. The cis-Az-H4 isomer showed stronger potency than the trans-Az-H4 against both the 6 Hz-induced psychomotor seizures and tonic-clonic seizures in the maximal electroshock test with 100 % protection demonstrated at the lowest dose of 1 μg administered intracerebroventricularly in mice. The effect of 1 and 5 μg cis-Az-H4 and 5 μg trans-Az-H4 was comparable to the positive control valproate in the 6-Hz test. None of the tested isomers displayed neurotoxicity in the rotarod test. Our results suggest that modified biopeptide in the N-terminus of hemorphin-4 with azobenzene deserve further exploration as a promising candidate with both anticonvulsant activity and as a chemosensor for pH determination.