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

Praveen Praveen; Ross AD Bathgate; Mohammed Akhter Hossain

Journal article

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

Praveen Praveen, Ross AD Bathgate, Mohammed Akhter Hossain

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | 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

Akhter Hossain Author Florey Department of Neuroscience and Mental Health

Ross Bathgate Author Florey Department of Neuroscience and Mental Health

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Grants

Awarded by NHMRC (Australia)

Awarded by A.R.C. linkage grant

Awarded by Australian Research Council

Awarded by National Health and Medical Research Council of Australia

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.