A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1

Mohammed Akhter Hossain; Martina Kocan; Song T Yao; Simon G Royce; Vinojini B Nair; Christopher Siwek; Nitin A Patil; Ian P Harrison; K Johan Rosengren; Stavros Selemidis; Roger J Summers; John D Wade; Ross AD Bathgate; Chrishan S Samuel

Journal article

A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1

Mohammed Akhter Hossain, Martina Kocan, Song T Yao, Simon G Royce, Vinojini B Nair, Christopher Siwek, Nitin A Patil, Ian P Harrison, K Johan Rosengren, Stavros Selemidis, Roger J Summers, John D Wade, Ross AD Bathgate, Chrishan S Samuel

CHEMICAL SCIENCE | ROYAL SOC CHEMISTRY | Published : 2016

DOI: 10.1039/c5sc04754d

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Abstract

Human gene-2 relaxin (H2 relaxin) is a pleiotropic hormone with powerful vasodilatory and anti-fibrotic properties which has led to its clinical evaluation and provisional FDA approval as a treatment for acute heart failure. The diverse effects of H2 relaxin are mediated via its cognate G protein coupled-receptor (GPCR), Relaxin Family Peptide Receptor (RXFP1), leading to stimulation of a combination of cell signalling pathways that includes cyclic adenosine monophosphate (cAMP) and extracellular-signal-regulated kinases (ERK)1/2. However, its complex two-chain (A and B), disulfide-rich insulin-like structure is a limitation to its facile preparation, availability and affordability. Furtherm..

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University of Melbourne Researchers

Song Yao Author Anatomy and Physiology

Akhter Hossain Author Florey Department of Neuroscience and Mental Health

Chrishan Samuel Author Biochemistry and Pharmacology

Ross Bathgate Author Florey Department of Neuroscience and Mental Health

John Wade Author Florey Department of Neuroscience and Mental Health

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Awarded by Australian Future Fellowships

Funding Acknowledgements

This work was supported by National Health & Medical Research Council (NHMRC) of Australia Grants (GNT1023321, GNT1023078, and GNT1065481) awarded to M. A. H., J. D. W., K. J. R., and R. A. D. B., (GNT1050268 and GNT1079680) awarded to S. T. Y., a NHMRC Program Grant GNT1055134 and ARC Linkage grant LP110100288 to R. J. S., a Florey Foundation Fellowship and Melbourne Research Grant Support Scheme (RGSS) awarded to M. A. H., a University of Melbourne Postgraduate Scholarship to V. B. N. and N. A. P., an Australian Postgraduate Award to C. S., Australian Future Fellowships to K. J. R. (FT130100890) and S. S. (FT120100876), an NHMRC Principal Research Fellowship to J. D. W. (GNT5018148) and NHMRC Senior Research Fellowships to R. A. D. B. (GNT1042650) and C. S. S. (GNT1041766). Research at The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program. We sincerely thank Mr Sharon Layfield, Ms Tania Ferraro and Ms Kazi Jannatul Ferdous for expert technical assistance; Associate Professor Tim Hewitson (Royal Melbourne Hospital, Melbourne, Australia) for providing the rat renal myofibroblasts; and Professor Robert Widdop (Monash University, Melbourne, Australia) for providing the PD123319.