Poster Presentation 6th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2017

Novel, modified dynorphin peptides for chronic pain and inflammation (#54)

Durga Prasad Yarra 1 , Karnaker R. Tupally 1 , Peter J. Cabot 1 , Paul N. Shaw 1 , Harendra S. Parekh 1
  1. Pharmacy Australia Centre of Excellence, Brisbane, QUEENSLAND, Australia

Opioids are the most commonly prescribed drugs for the management of chronic pain and inflammatory diseases. However, severe adverse effects like addiction, respiratory depression and constipation limit their clinical use. Recent evidence indicates that endogenous opioid peptides, especially kappa opioid receptor selective agonists produce pronounced antinociception without the rampant side effects associated with marketed opioids. Dynorphin A (1-17) is a selective kappa opioid receptor agonist and reports suggest that metabolic fragments of dynorphin A (1-17) are involved in the control of chronic inflammatory pain. As the inherent instability of exogenously administered peptides in biological system is a major obstacle in bringing the peptides to market, we aim to transform native dynorphin A (1-17) into constructs demonstrating greater resilience to endogenous enzymes. In our preliminary study, we synthesized a diverse library of conformationally constrained analogues of dynorphin A (1-17) using Fmoc-based solid phase peptide synthesis protocols. The synthesized peptides were characterized by LC-MS, and investigated for stability in serum at 37 °C. Analogues have demonstrated enhanced stability in rat serum compared to the corresponding linear peptides. Further enzymatic and cell-based assays are underway to confirm their stability and pharmacological efficacy in cellular models of pain and inflammation.