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

A single-chain derivative of the relxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1 (#55)

Praveen Praveen 1 , Ross Bathgate 1 , M. Akhter Hossain 1 , Nitin Patil 1
  1. Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia

H2-relaxin is therapeutically very important due to its strong vasoprotective and vasodilatory effects. However, the synthesis of the recombinant form of the peptides is laborious and time consuming. Thus, simpler H2-relaxin analogoues are needed. Based on extensive SAR studies done in our lab, we have developed single chain derivative of H2-relaxin known as B7-33. This peptide was tested in rat renal myofibroblasts (from injured kidneys) and human cardiac fibroblasts (endogenously expressing RXFP1 cells) for its ability to promote matrix metalloproteinase (MMP-2), a collagen-degrading enzyme, and was found to exhibit similar potency to H2 relaxin. Most importantly, like H2 relaxin, B7-33 reversed or cured fibrosis in three animal models (rat vs mouse; heart fibrosis vs lung fibrosis). Based on these exciting results, I will use B7-33 as a template to further develop this peptide by improving its potency and pharmacokinetics.