Tripeptide Phe-Trp-Leu-NH2 as a putative endogenous ligand of TSPO: molecular modeling, synthesis and pharmacological activity

Abstract

The putative endogenous tripeptide ligand of the translocator protein (TSPO) l-phenylalanyl-l-tryptophanyl-l-leucine amide was obtained using the drug-based peptide design strategy and molecular modeling. This tripeptide demonstrated anxiolytic activity in the elevated plus-maze test and antidepressant-like activity in the forced swimming test in BALB/c mice at the doses of 10 mg kg⁻¹ (i.p.) and also showed neuroprotective activity in the concentration range of 10⁻⁵–10⁻⁷ m in vitro under conditions of oxidative stress using HT-22 neuronal cell line.