Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/28040
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dc.contributor.authorLiu, Mengjie-
dc.contributor.authorWhite, Barbara F-
dc.contributor.authorPraveen, Praveen-
dc.contributor.authorLi, Wenyi-
dc.contributor.authorLin, Feng-
dc.contributor.authorWu, Hongkang-
dc.contributor.authorLi, Rong-
dc.contributor.authorDelaine, Carlie-
dc.contributor.authorForbes, Briony E-
dc.contributor.authorWade, John D-
dc.contributor.authorHossain, Mohammed Akhter-
dc.date2021-
dc.date.accessioned2021-11-22T05:10:51Z-
dc.date.available2021-11-22T05:10:51Z-
dc.date.issued2021-
dc.identifier.citationJournal of medicinal chemistry 2021; 64(23): 17448-17454en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/28040-
dc.description.abstractThe growing epidemic of diabetes means that there is a need for therapies that are more efficacious, safe, and convenient. Here, we report the efficient synthesis of a novel disulfide dimer of human insulin tethered at the N-terminus of its B-chain through placement of a cysteine residue. The resulting peptide was shown to bind to both the insulin receptor isoform B and insulin-like growth factor-1 receptor with comparable affinity to native insulin. In in vivo insulin tolerance tests, the dimer was equipotent to Actrapid insulin and possessed a sustained duration of action greater than that of Actrapid and Glargine. While the secondary structure of our dimeric insulin was similar to that of insulin, it was more resistant to proteolysis. More importantly, our analogue was produced in quantitative yield from a monomeric thiol insulin scaffold. Our results suggest that this dimer has significant potential to address the clinical needs in the treatment of diabetes.en
dc.language.isoeng-
dc.titleEngineering of a Biologically Active Insulin Dimer.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of medicinal chemistryen
dc.identifier.affiliationSchool of Chemistry, The University of Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationMedicineen
dc.identifier.affiliationDiscipline of Medical Biochemistry, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia 5042, Australiaen
dc.identifier.affiliationThe Florey Department of Neuroscience and Mental Health, The University Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationAustin Healthen
dc.identifier.doi10.1021/acs.jmedchem.1c01594en
dc.type.contentTexten
dc.identifier.orcid0000-0003-1944-5301en
dc.identifier.orcid0000-0001-9068-6357en
dc.identifier.orcid0000-0003-3584-0301en
dc.identifier.orcid0000-0001-5735-4924en
dc.identifier.orcid0000-0003-4360-9927en
dc.identifier.orcid0000-0002-1352-6568en
dc.identifier.orcid0000-0002-9961-0006en
dc.identifier.pubmedid34797669-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
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