Single-Shot Solid-Phase Synthesis of Full-Length H2 Relaxin Disulfide Surrogates
Single-Shot Solid-Phase Synthesis of Full-Length H2 Relaxin Disulfide Surrogates
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DOI：
10.1002/anie.202216365
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发表时间：
2023-01-09
影响因子：
16.6
通讯作者：
Liu，Lei
中科院分区：
文献类型：
--
作者：
Zhao，Rui;Shi，Pan;Liu，Lei
胰岛素超家族蛋白（ISP）的化学合成最近被广泛研究，以开发下一代药物。这些研究中通常会遇到多个肽片段的单独合成和繁琐的链对链折叠，限制了 ISP 衍生物的可及性。在这里，我们报告了这样的发现：在 A-B 链末端二硫键处掺入预制二氨基二酸桥的胰岛素超家族蛋白（例如 H2 松弛素、胰岛素本身和 H3 松弛素）可以通过单次自动化固相合成和便捷的一步折叠轻松快速地合成。与天然对应物相比，我们的新型 H2 松弛素类似物表现出几乎相同的结构和活性。这种新的合成策略将加快用于药物研究的新 ISP 类似物的生产。
Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next‐generation drugs. Separate synthesis of multiple peptide fragments and tedious chain‐to‐chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre‐made diaminodiacid bridge at A‐B chain terminal disulfide can be easily and rapidly synthesized by a single‐shot automated solid‐phase synthesis and expedient one‐step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies.