Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4

P Praveen; RAD Bathgate; MA Hossain

Journal article

Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4

P Praveen, RAD Bathgate, MA Hossain

Scientific Reports | NATURE PORTFOLIO | Published : 2019

DOI: 10.1038/s41598-019-53707-z

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Abstract

Insulin-like peptide 5 (INSL5) is a very important pharma target for treating human conditions such as anorexia and diabetes. However, INSL5 with two chains and three disulfide bridges is an extremely difficult peptide to assemble by chemical or recombinant means. In a recent study, we were able to engineer a simplified INSL5 analogue 13 which is a relaxin family peptide receptor 4 (RXFP4)-specific agonist. To date, however, no RXFP4-specific antagonist (peptide or small molecule) has been reported in the literature. The focus of this study was to utilize the non-specific RXFP3/RXFP4 antagonist ΔR3/I5 as a template to rationally design an RXFP4 specific antagonist. Unexpectedly, we demonstra..

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University of Melbourne Researchers

Ross Bathgate Author

Akhter Hossain Author

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Grants

Awarded by Australian Research Council

Funding Acknowledgements

This research was partly funded by NHMRC (Australia) project grants (1023321, 1065481, and 1023078) to M.A.H., R.A. D.B. and A.R.C. linkage grant (LP120100654) to M.A.H. and R.A.D. B. We are grateful to Tania Ferraro and Sharon Layfield for assistance with biochemical assays. RADB is an NHMRC Senior Research Fellow. Studies at the Florey Institute were supported by the Victorian Government's Operational Infrastructure Support Program.