Journal article

Effects of C-Terminal B-Chain Modifications in a Relaxin 3 Agonist Analogue

Praveen Praveen, Julien Tailhades, K Johan Rosengren, Mengjie Liu, John D Wade, Ross AD Bathgate, Mohammed Akhter Hossain

ACS Medicinal Chemistry Letters | AMER CHEMICAL SOC | Published : 2020

Abstract

The receptor for the neuropeptide relaxin 3, relaxin family peptide 3 (RXFP3) receptor, is an attractive pharmacological target for the control of eating, addictive, and psychiatric behaviors. Several structure-activity relationship studies on both human relaxin 3 (containing 3 disulfide bonds) and its analogue A2 (two disulfide bonds) suggest that the C-terminal carboxylic acid of the tryptophan residue in the B-chain is important for RXFP3 activity. In this study, we have added amide, alcohol, carbamate, and ester functionalities to the C-terminus of A2 and compared their structures and functions. As expected, the C-terminal amide form of A2 showed lower binding affinity for RXFP3 while es..

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Grants

Awarded by NHMRC Research Fellowships


Awarded by NHMRC Project Grant


Funding Acknowledgements

J.D.W. and R.A.D.B. are recipients of NHMRC Research Fellowships (1117483 and 1135837, respectively). K.J.R. and R.A.D.B. were supported by an NHMRC Project Grant (1165801). Studies at the Florey Institute were supported by the Victorian Government's Operational Infrastructure Support Program.