Williams Geoffrey M, Lee Kathryn, Li Xun, Cooper Garth J S, Brimble Margaret A
The School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland 1010, New Zealand.
Org Biomol Chem. 2015 Apr 7;13(13):4059-63. doi: 10.1039/c5ob00160a.
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.
利用铜催化的叠氮-炔环加成点击化学制备了两种甘精胰岛素类似物，其中用1,4-二取代的1,2,3-三唑基团取代了CysA7-CysB7二硫键，以有效地连接肽链。通过圆二色光谱对所得胰岛素类似物进行分析，以评估这种修饰是否会破坏天然形式的折叠模式。包括体内小鼠研究在内的调查表明，这些类似物没有生物活性，并且结构明显解折叠，这一结果表明维持精确的链间距离对胰岛素激素的结构至关重要。
