title: Chemical synthesis and orexigenic activity of rat/mouse relaxin-3.
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.
authors: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, 3010, Australia. akhter.hossain@unimelb.edu.au
authors: Mohammed Akhter
authors: MA
authors: Hossain
authors: Craig M
authors: CM
authors: Smith
authors: Philip J
authors: PJ
authors: Ryan
authors: Elena
authors: E
authors: Büchler
authors: Ross A D
authors: RA
authors: Bathgate
authors: Andrew L
authors: AL
authors: Gundlach
authors: John D
authors: JD
authors: Wade
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004220:Disulfides; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012065:Relaxin / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D004220:Disulfides; D009419:Nerve Tissue Proteins; C466742:RLN3 protein, rat; D043562:Receptors, G-Protein-Coupled; C512898:relaxin-3 protein, mouse; D012065:Relaxin