The chemical synthesis of insulin is an enduring challenge due to the hydrophobic peptide chains and construction of the correct intermolecular disulfide pattern. We report a new approach to the chemical synthesis of insulin using a short, traceless, prosthetic C-peptide that facilitates the formation of the correct disulfide pattern during folding and its removal by basic treatment. The linear precursor is assembled by an ester forming α-ketoacid-hydroxylamine (KAHA) ligation that provides access to the linear insulin precursors in good yield from two readily prepared segments. This convergent and flexible route provides access to various human, mouse, and guinea pig insulins containing a single homoserine mutation that shows no detrimental effect on the biological activities.

中文翻译：

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通过α-酮酸-羟胺（KAHA）连接制备的带有人工C肽的胰岛素变体的折叠方便†

由于疏水性肽链和正确的分子间二硫键模式的构建，胰岛素的化学合成是一项持久的挑战。我们报告了一种使用短的，无痕的，义肢的C肽进行胰岛素化学合成的新方法，该肽在折叠过程中有助于形成正确的二硫键模式，并通过基本处理将其去除。线性前体是通过形成α-酮酸-羟胺（KAHA）的酯的组装而组装的，该连接提供了从两个易于制备的链段以高收率获得线性胰岛素前体的途径。这种收敛而灵活的途径使人们能够获得各种含有单一高丝氨酸突变的人，小鼠和豚鼠胰岛素，而这些突变对生物活性没有有害影响。