Review of the article „Gram-scale preparation of C-terminal modified enkephalin analogues by typical liquid-phase peptide synthesis“, verified by Publons, Web of Science

Abstract

This protocol describes the gram-scale liquid-phase peptide synthesis of C-terminal modified enkephalin analogues. The C-terminus of enkephalin was modified by a moiety of fentanyl, N-phenyl-N-(piperidin-4-yl)-propionamide to acquire synergistic effects with mixed opioid receptor activities and to optimize metabolic stability and blood brain barrier penetration with lipophilic moiety substitution. Lead compounds showed high analgesic efficacy in nerve injured animal models with strong binding affinity at mu and delta opioid receptors. The preparation of large quantity of analogues were done by liquid phase peptide synthesis established for long period in the laboratory. Obviously, liquid phase synthesis even with long cycle time and purification step is ideal for the large-scale synthesis of peptides owing to cost effectiveness and easy detection of impurity profile compared to solid phase synthesis. Here the author shows a robotic liquid phase synthesis involving Bop-assisted coupling and Boc-deprotection for the gram-scale synthesis of C-terminal modified enkephalin analogues, which establishes a way to produce peptide drugs cost-effectively.