Solid phase peptide synthesis (SPPS) strategy based on diaminodiacids had become an effective method for the synthesis of disulfide‐containing polypeptides. At present, it remains necessary to develop a diaminodiacid with more abundant chain structures to study the structure‐activity relationship. In this work, we developed a new type of diaminodiacids containing a six‐atom thioether (C−C‐S−C‐C−C, C−C‐C−S‐C−C) bridge. The key segment protected homo‐homocystine can be efficiently obtained by converting a side chain carboxyl group into a thiol group, which contribute to the facile and efficient synthesis of new diaminodiacid. With this diaminodiacid in hand, we successfully obtained tachyplesin containing new disulfide bond mimic by solid phase peptide synthesis. The tachyplesin analog not only has similar activity as natural counterpart, but also exhibits increased stability under reducing conditions.

中文翻译：

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六原子硫醚桥联二氨基二酸的化学合成用于肽二硫键模拟物的固相合成

基于二氨基二酸的固相肽合成（SPPS）策略已成为合成含二硫键多肽的有效方法。目前，仍需要开发链结构更丰富的二氨基二酸来研究其结构活性关系。在这项工作中，我们开发了一种新型的含有六原子硫醚（CC-SC-CC-CC，CC-CC-SC）桥的二氨基二酸。通过将侧链羧基转化为硫醇基团可以有效地获得关键片段保护的高同型半胱氨酸，这有助于新二氨基二酸的简便有效合成。有了这种二氨基二酸，我们通过固相肽合成成功地获得了含有新的二硫键模拟物的速激肽。速激肽类似物不仅具有与天然类似物相似的活性，