Enzymatically forming cell compatible supramolecular assemblies of tryptophan‐rich short peptides,Peptide Science

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Enzymatically forming cell compatible supramolecular assemblies of tryptophan‐rich short peptides
Peptide Science ( IF 1.5 ) Pub Date : 2020-06-02 , DOI: 10.1002/pep2.24173
Dongsik Yang ₁ , Beom Jin Kim ₁ , Hongjian He ₁ , Bing Xu ₁

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Here, we report a new type of tryptophan‐rich short peptides, which act as hydrogelators, form supramolecular assemblies via enzymatic dephosphorylation, and exhibit cell compatibility. The facile synthesis of the peptides starts with the production of phosphotyrosine and then uses solid‐phase peptide synthesis to build the phosphopeptides that contain multiple tryptophan residues. Besides exhibiting excellent solubility, these phosphopeptides, unlike the previously reported cytotoxic phenylalanine‐rich phosphopeptides, are largely compatible toward mammalian cells. Our preliminary mechanistic study suggests that the tryptophan‐rich peptides, instead of forming pericellular assemblies, largely accumulate in lysosomes. Such lysosomal localization may account for their cell compatibility. Moreover, these tryptophan‐rich peptides are able to transiently reduce the cytotoxicity of phenylalanine‐rich peptide assemblies. This rather unexpected result implies that tryptophan may act as a useful aromatic building block for developing cell compatible supramolecular assemblies for soft materials and find applications for protecting cells from cytotoxic peptide aggregates.

中文翻译：

富含色氨酸的短肽酶促形成细胞相容的超分子组装体

在这里，我们报告了一种新型的富含色氨酸的短肽，它作为水凝胶剂，通过酶促去磷酸化形成超分子组装体，并表现出细胞相容性。肽的简便合成从产生磷酸酪氨酸开始，然后使用固相肽合成来构建含有多个色氨酸残基的磷酸肽。除了表现出优异的溶解性外，这些磷酸肽与之前报道的富含细胞毒性苯丙氨酸的磷酸肽不同，它们在很大程度上与哺乳动物细胞相容。我们的初步机制研究表明，富含色氨酸的肽不会形成细胞周围的组装体，而是大量积聚在溶酶体中。这种溶酶体定位可能解释了它们的细胞相容性。而且，这些富含色氨酸的肽能够暂时降低富含苯丙氨酸的肽组装体的细胞毒性。这一相当出乎意料的结果表明，色氨酸可以作为一种有用的芳香族结构单元，用于开发用于软材料的细胞相容性超分子组装体，并找到保护细胞免受细胞毒性肽聚集体的应用。

更新日期：2020-06-02

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