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
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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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.