Exploring the Use of Helicogenic Amino Acids for Optimising Single Chain Relaxin-3 Peptide Agonists
Han Siean Lee, Shu Hui Wang, James T Daniel, Mohammed Akhter Hossain, Richard J Clark, Ross AD Bathgate, K Johan Rosengren
Biomedicines | MDPI | Published : 2020
Relaxin-3 is a highly conserved two-chain neuropeptide that acts through its endogenous receptor the Relaxin Family Peptide-3 (RXFP3) receptor. The ligand/receptor system is known to modulate several physiological processes, with changes in food intake and anxiety-levels the most well studied in rodent models. Agonist and antagonist analogues based on the native two-chain peptide are costly to synthesise and not ideal drug leads. Since RXFP3 interacting residues are found in the relaxin B-chain only, this has been the focus of analogue development. The B-chain is unstructured without the A-chain support, but in single-chain variants structure can be induced by dicarba-based helical stapling ..View full abstract
Awarded by National Health and Medical Research Council (NHMRC), Australia
Awarded by NHMRC
This research was funded by National Health and Medical Research Council (NHMRC), Australia, Project Grant 1165801 (to K.J.R. and R.A.D.B.) and NHMRC Research Fellowship (1135837) (to R.A.D.B.). Studies at the Florey Institute were supported by the Victorian Government's Operational Infrastructure Support Program.