Synthetic covalently linked dimeric form of h2 relaxin retains native RXFP1 activity and has improved in vitro serum stability

VB Nair; RAD Bathgate; F Separovic; CS Samuel; MA Hossain; JD Wade

Journal article

Synthetic covalently linked dimeric form of h2 relaxin retains native RXFP1 activity and has improved in vitro serum stability

VB Nair, RAD Bathgate, F Separovic, CS Samuel, MA Hossain, JD Wade

Biomed Research International | HINDAWI LTD | Published : 2015

DOI: 10.1155/2015/731852

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Abstract

Human (H2) relaxin is a two-chain peptide member of the insulin superfamily and possesses potent pleiotropic roles including regulation of connective tissue remodeling and systemic and renal vasodilation. These effects are mediated through interaction with its cognate G-protein-coupled receptor, RXFP1. H2 relaxin recently passed Phase III clinical trials for the treatment of congestive heart failure. However, its in vivo half-life is short due to its susceptibility to proteolytic degradation and renal clearance. To increase its residence time, a covalent dimer of H2 relaxin was designed and assembled through solid phase synthesis of the two chains, including a judiciously monoalkyne sited B-..

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University of Melbourne Researchers

Ross Bathgate Author

Frances Separovic Author

Akhter Hossain Author

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Funding Acknowledgements

This research was partially funded by National Health and Medical Research Council (NHMRC) of Australia Project Grants 508995 and 1023078 to John D. Wade, Mohammed Akhter Hossain, and Ross A. D. Bathgate. The authors thank Tania Ferraro and Sharon Layfield for their assistance in undertaking the biological assays. Mohammed Akhter Hossain was the recipient of a Florey Foundation Fellowship and Ross A. D. Bathgate (APP1042650) and Chrishan S. Samuel (APP1041766) are NHMRC Senior Research Fellows, and John D. Wade (APP5018148) is an NHMRC Principal Research Fellow. Research at The Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program.