Synthesis and Biological Activity of Conformational Restricted Galanin Fragments

摘要

Since the discovery of galanin (Gal) by Tatemoto et al [1], this neuropeptide has obtained increasing interest, mainly motivated by its widespread distribution and involvement in a multitude of physiological actions, such as central cardiovascular control, control of appetite and seizures, effects on pain and depression. Pharmacological tools to fully examine the actions of galanin and its receptors are still lacking and need to be better explored [2]. Galanin consists of 29 amino acid (30 in humans) residues and the N-terminal part (1-16) of the peptide has proven crucial for Gal's bioactivity [3]. A number of attempts have been made to design chimeric peptides as ligands for the receptors. One of the limitations of the pharmacological use of peptide ligands is due to their short half-lives and poor bioavailability in the CNS. Inclusion of a lactam bridge in the peptides sequence is one strategy employed in an attempt to promote peptide degradation resistance and also structure stabilization [2].