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Chemical synthesis and orexigenic activity of rat/mouse relaxin-3

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Abstract

The insulin-like peptide, relaxin-3 was first identified just a decade ago via a genomic database search and is now recognized to be a key neuropeptide with several roles including the regulation of arousal, stress responses and neuroendocrine homeostasis. It also has significant potential as a drug to treat stress and obesity. Its actions are mediated via its cognate G protein-coupled receptor, RXFP3, which is found in abundant numbers in the brain. However, much remains to be determined with respect to the mechanism of neurological action of this peptide. Consequently, the chemical synthesis of the rat and mouse (which share identical primary structures) two-chain, three disulfide peptide was undertaken and the resulting peptide subjected to detailed in vitro and in vivo assay. Use of efficient solid-phase synthesis methods provided the two regioselectively S-protected A- and B-chains which were readily combined via sequential disulfide bond formation. The synthetic rat/mouse relaxin-3 was obtained in high purity and good overall yield. It demonstrated potent orexigenic activity in rats in that central intracerebroventricular infusion led to significantly increased food intake and water drinking.

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Acknowledgments

This research was funded by NHMRC (Australia) project Grants 508995, and 1023078 to JDW, MAH and RADB and 1005988 to ALG and RADB. We are grateful to Tania Ferraro and Sharon Layfield for assistance with biochemical assays and to Feng Lin for amino acid analysis. MAH was the recipient of a Florey Foundation Fellowship and RADB, ALG and JDW are NHMRC (Australia) Research Fellows. Research at the Florey Institute of Neuroscience and Mental Health is supported by the Victorian Government Operational Infrastructure Support Program.

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Author notes

  1. Elena Büchler

    Present address: Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany

Authors and Affiliations

  1. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia

    Mohammed Akhter Hossain, Craig M. Smith, Philip J. Ryan, Elena Büchler, Ross A. D. Bathgate, Andrew L. Gundlach & John D. Wade

  2. Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia

    Mohammed Akhter Hossain, Ross A. D. Bathgate, Andrew L. Gundlach & John D. Wade

  3. School of Chemistry, The University of Melbourne, Victoria, 3010, Australia

    Mohammed Akhter Hossain & John D. Wade

  4. Department of Anatomy and Neuroscience, The University of Melbourne, Victoria, 3010, Australia

    Craig M. Smith, Philip J. Ryan & Andrew L. Gundlach

  5. Department of Biochemistry and Molecular Biology, The University of Melbourne, Victoria, 3010, Australia

    Ross A. D. Bathgate

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  1. Mohammed Akhter Hossain
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Correspondence to Mohammed Akhter Hossain or John D. Wade.

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Hossain, M.A., Smith, C.M., Ryan, P.J. et al. Chemical synthesis and orexigenic activity of rat/mouse relaxin-3. Amino Acids 44, 1529–1536 (2013). https://doi.org/10.1007/s00726-013-1478-0

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  • DOI: https://doi.org/10.1007/s00726-013-1478-0

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