SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION
SYNTHESIS OF PROTEINS BY NATIVE CHEMICAL LIGATION
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DOI：
10.1126/science.7973629
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发表时间：
1994-11-04
期刊：
影响因子：
56.9
通讯作者：
KENT, SBH
中科院分区：
文献类型：
--
作者：
DAWSON, PE;MUIR, TW;KENT, SBH
已经设计了一种简单的技术，该技术允许直接合成中等大小的天然骨干蛋白。两个未受保护的肽段的化学选择性反应可提供最初的硫酯连接物种。该瞬态中间体的自发重排产生的全长产物在连接部位带有天然肽键。一步制剂的细胞因子含有多种二硫化物，证明了天然化学连接的效用。将多肽连接产物折叠并氧化以形成含天然二硫化物的蛋白质分子。天然化学结扎是迈向化学对蛋白质的一般应用的重要一步。
A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transient intermediate yields a full-length product with a native peptide bond at the ligation site. The utility of native chemical ligation was demonstrated by the one-step preparation of a cytokine containing multiple disulfides. The polypeptide ligation product was folded and oxidized to form the native disulfide-containing protein molecule. Native chemical ligation is an important step toward the general application of chemistry to proteins.