The study of biodegradation of galanin and its N-terminal fragments in a model system in vitro.

Exogenous N-terminal fragments of galanin, which are agonists of the GalR2 receptor, have therapeutic potential in experimental cardiac pathology. This implies the need to study their proteolytic stability in biological environments. The aim of this work was to evaluate the proteolytic degradation of galanin G1 (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2), its natural and modified fragments G2 and G3 (WTLNSAGYLLGPHA-OH and WTLNSAGYLLGPβAH-OH, respectively) in human plasma. The peptides were obtained by solid-phase synthesis using the Fmoc methodology, purified by HPLC; their structure was confirmed by MALDI-TOF mass spectrometry and 1H-NMR spectroscopy. The kinetics of galanins G1-G3 degradation in blood plasma was studied by 1H-NMR spectroscopy based on changes in the intensity of Trp2 signals at 310 K. The results indicate a higher proteolytic stability of the G3 peptide compared to the natural G2 fragment and full-length galanin G1. They indicate the potential of using modified peptide agonists of GalR2 receptors to protect vital organs in pathophysiological conditions.