Replacement of the CysA7-CysB7 disulfide bond with a 1,2,3-triazole linker causes unfolding in insulin glargine

Organic & Biomolecular Chemistry
Geoffrey M WilliamsMargaret A Brimble

Abstract

Two analogues of insulin glargine containing a 1,4-disubstituted 1,2,3-triazole group in place of the CysA7-CysB7 disulfide bond were prepared using CuAAC click chemistry to efficiently join the peptide chains. The resulting insulin analogues were analysed by circular dichroism spectroscopy to assess whether this modification compromised the folding pattern of the native form. Investigations, including an in vivo murine study, revealed that these analogues were not biologically active and that the structures were significantly unfolded, an outcome which suggests that maintaining a precise inter-chain distance is critical to the structure of the insulin hormone.

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Jan 23, 2016·Scientific Reports·Jitka VikováJiří Jiráček
May 15, 2015·Organic & Biomolecular Chemistry·Surendar Reddy BathulaSrivari Chandrasekhar
Jul 28, 2017·Chemistry : a European Journal·Alessandro GoriSilvia Rinaldi
Feb 8, 2020·Angewandte Chemie·Claudia E MurarJeffrey W Bode
Aug 16, 2018·MedChemComm·H ChilukuriM Fernandes
Mar 11, 2021·Chemical Reviews·John A KarasMohammed Akhter Hossain
Dec 6, 2019·Journal of Medicinal Chemistry·Nan ZhengDanny Hung-Chieh Chou
Aug 23, 2017·Accounts of Chemical Research·Mohammed Akhter Hossain, John D Wade

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