Keywords : Drug Design
Design of chimeric neuropeptide analogues based on galanin and substance P to obtain a possible effect in the treatment of Major depressive disorder
European Journal of Molecular & Clinical Medicine,
2020, Volume 7, Issue 2, Pages 4772-4779
Major depressive disorder (MDD) and anxiety are two of the principal psychiatric disorders that affect humans and whose treatment is under current investigation. There are vast amounts of brain neuropeptides, which show the potential of becoming unique therapeutic targets. Some studies have reported the effects of neuropeptide structural analogues on certain depression-like behaviors.
Galanin (GAL) and substance P (SP) act as regulatory peptides that have been linked to several physiological functions, which include anxiolytic and antidepressant activities. These effects are mediated through G protein-coupled receptors (GPCRs) displaying a diversity of signal transduction pathways.
In this project the design, synthesis and effects of several chimeric and non-chimeric analogues of the neuropeptides galanin and substance P are described. Four methods were used throughout the project: microwave-assisted solid-phase synthesis (SPPS) to synthetize the chimeric analogues, high-performance liquid chromatography (HPLC) to purify the crude molecules, electrospray ionization mass spectrometry (ESI-MS) to verify the theoretical molecular weight of the analogues and radioligand competition binding studies to assess the neuropharmacological activity of the ligands.
Results showed some inconsistencies related to synthesis, purification and characterization of the ligands most likely due to technical and operational problems, so they cannot be taken as conclusive without further optimization of the techniques. After achieving optimization, the ligands tested might potentially work as therapeutic drugs for in vivo studies (using animal models) and hopefully even reach pre-clinical and clinical trials in the future.