Discovery of IL-5-binding unnatural cyclic peptides from multiple libraries by directed evolution
Discovery of IL-5-binding unnatural cyclic peptides from multiple libraries by directed evolution
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通过定向进化从多个文库中发现 IL-5 结合非天然环肽
DOI：
10.1016/j.bbrc.2022.04.043
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发表时间：
2022
影响因子：
3.1
通讯作者：
Kawakami Takashi
中科院分区：
文献类型：
--
作者：
Fuji Daisuke;Ando Takehiro;Sato Masashi;Vedi Santhana;Takamori Yukio;Yokoyama Takumi;Yamamoto Mizuki;Kawakami Takashi
白介素5(IL-5)是一种2型细胞因子，参与多种过敏性疾病，包括严重的嗜酸性哮喘。在这项研究中，我们使用指数富集型配体的系统进化(SELEX)从多个mRNA展示的多肽库中针对人IL-5进行了定向进化。用基于大肠杆菌的重组无细胞转录和翻译偶联系统(纯系统)构建多肽文库，并使用多个分子内具有硫醇活性的苯甲酸连接物自发环化，这些连接物通过遗传密码扩展以核糖体形式并入。我们从多个高度多样化的mRNA展示文库中成功地鉴定了多个具有不同环化接头的新型IL-5结合非天然环肽。还进行了化学二聚反应，以增加非天然环状IL-5结合肽的亲和力。本研究发现的新型IL-5结合非天然环肽可用于涉及IL-5信号转导的各种研究、治疗和诊断应用。
Interleukin-5 (IL-5) is a type 2 cytokine involved in various allergic diseases, including severe eosinophilic asthma. In this study, we performed directed evolution against human IL-5 using systematic evolution of ligands by exponential enrichment (SELEX) from multiple mRNA-displayed peptide libraries. Peptide libraries were prepared withEscherichia coli-based reconstituted cell-free transcription and translation coupling system (PURE system) and spontaneously cyclized using multiple intramolecularly thiol-reactive benzoic acid-derived linkers, which were ribosomally incorporated through genetic code expansion. We successfully identified multiple novel IL-5-binding unnatural cyclic peptides with different cyclization linkers from multiple highly diverse mRNA-displayed libraries. Chemical dimerization was also performed to increase the avidity of unnatural cyclic IL-5-binding peptides. The novel IL-5-binding unnatural cyclic peptides discovered in this study could be used in various research, therapeutic, and diagnostic applications involving IL-5 signaling.