title: Minimum active structure of insulin-like peptide 5.
abstract: Insulin-like peptide 5 (INSL5) is a complex two-chain peptide hormone constrained by three disulfide bonds in a pattern identical to insulin. High expression of INSL5 in the colon suggests roles in activation of colon motility and appetite control. A more recent study indicates it may have significant roles in the regulation of insulin secretion and β-cell homeostasis. This peptide thus has considerable potential for the treatment of eating disorders, obesity, and/or diabetes. However, the synthesis of INSL5 is extremely challenging either by chemical or recombinant means. The A-chain is very poorly soluble and the B-chain is highly aggregating in nature which, together, makes their postsynthesis handling and purification very difficult. Given these difficulties, we have developed a highly active INSL5 analogue that has a much simpler structure with two disulfide bonds and is thus easier to assemble compared to native INSL5. This minimized peptide represents an attractive new mimetic for investigating the functional role of INSL5.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, ‡Department of Biochemistry and Molecular Biology, §Florey Department of Neuroscience and Mental Health, and ∥School of Chemistry, The University of Melbourne , Victoria 3010, Australia.
authors.forename: Alessia
authors.initials: A
authors.lastname: Belgi
authors.forename: Ross A D
authors.initials: RA
authors.lastname: Bathgate
authors.forename: Martina
authors.initials: M
authors.lastname: Kocan
authors.forename: Nitin
authors.initials: N
authors.lastname: Patil
authors.forename: Suode
authors.initials: S
authors.lastname: Zhang
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Tregear
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000502:physiology; D051379:Mice; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C480239:RXFP4 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D048049:Extracellular Signal-Regulated MAP Kinases