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dc.contributor.authorXiong, X
dc.contributor.authorMenting, JG
dc.contributor.authorDisotuar, MM
dc.contributor.authorSmith, NA
dc.contributor.authorDelaine, CA
dc.contributor.authorGhabash, G
dc.contributor.authorAgrawal, R
dc.contributor.authorWang, X
dc.contributor.authorHe, X
dc.contributor.authorFisher, SJ
dc.contributor.authorMacRaild, CA
dc.contributor.authorNorton, RS
dc.contributor.authorGajewiak, J
dc.contributor.authorForbes, BE
dc.contributor.authorSmith, BJ
dc.contributor.authorSafavi-Hemami, H
dc.contributor.authorOlivera, B
dc.contributor.authorLawrence, MC
dc.contributor.authorChou, DH-C
dc.identifierpii: 10.1038/s41594-020-0430-8
dc.identifier.citationXiong, X., Menting, J. G., Disotuar, M. M., Smith, N. A., Delaine, C. A., Ghabash, G., Agrawal, R., Wang, X., He, X., Fisher, S. J., MacRaild, C. A., Norton, R. S., Gajewiak, J., Forbes, B. E., Smith, B. J., Safavi-Hemami, H., Olivera, B., Lawrence, M. C. & Chou, D. H. -C. (2020). A structurally minimized yet fully active insulin based on cone-snail venom insulin principles. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 27 (7), pp.615-+.
dc.description.abstractHuman insulin and its current therapeutic analogs all show propensity, albeit varyingly, to self-associate into dimers and hexamers, which delays their onset of action and makes blood glucose management difficult for people with diabetes. Recently, we described a monomeric, insulin-like peptide in cone-snail venom with moderate human insulin-like bioactivity. Here, with insights from structural biology studies, we report the development of mini-Ins-a human des-octapeptide insulin analog-as a structurally minimal, full-potency insulin. Mini-Ins is monomeric and, despite the lack of the canonical B-chain C-terminal octapeptide, has similar receptor binding affinity to human insulin. Four mutations compensate for the lack of contacts normally made by the octapeptide. Mini-Ins also has similar in vitro insulin signaling and in vivo bioactivities to human insulin. The full bioactivity of mini-Ins demonstrates the dispensability of the PheB24-PheB25-TyrB26 aromatic triplet and opens a new direction for therapeutic insulin development.
dc.titleA structurally minimized yet fully active insulin based on cone-snail venom insulin principles
dc.typeJournal Article
melbourne.affiliation.departmentMedical Biology (W.E.H.I.)
melbourne.source.titleNature Structural and Molecular Biology
melbourne.openaccess.statusPublished version
melbourne.contributor.authorLawrence, Michael
melbourne.identifier.fundernameidAustralian Research Council, LE170100200
melbourne.accessrightsAccess this item via the Open Access location

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