Interleukin-17A Peptide Aptamers with an Unexpected Binding Moiety Selected by cDNA Display under Heterogenous Conditions
Interleukin-17A Peptide Aptamers with an Unexpected Binding Moiety Selected by cDNA Display under Heterogenous Conditions
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DOI：
10.1021/acsmedchemlett.1c00217
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发表时间：
2021-08-27
影响因子：
4.2
通讯作者：
Nemoto, Naoto
中科院分区：
文献类型：
--
作者：
Anzai, Hiroki;Terai, Takuya;Nemoto, Naoto
基于肽的药物是一种有吸引力的新的治疗方式，并且从大规模文库中进行体外选择是鉴定新的前导序列的有力方式。在常规筛选中，没有评估肽在生理异质环境中的特异性和稳定性，这有时使得后续优化困难。在这里，我们表明，使用cDNA展示系统的选择可以在高百分比的血清中进行，这可能是一种选择，以选择在生物学背景下具有高效力和稳定性的分子。具体而言，我们选择白细胞介素-17 A作为靶蛋白，并在血清存在下从约10（12）个成员的文库中进行环肽适体的体外选择。选择的分子具有纳摩尔亲和力的目标，并在血清中稳定。有趣的是，我们发现连接肽和cDNA的DNA接头的一个成分可能在靶点结合中发挥关键作用。
Peptide-based drugs are an attractive new modality of therapeutics, and in vitro selection from a large-scale library is a powerful way to identify new lead sequences. In conventional screenings, peptide specificity and stability in physiological heterogenous environments are not evaluated, which sometimes makes subsequent optimization difficult. Here we show that selection using a cDNA display system can be performed in a high percentage of serum and that this might be an option to select molecules with high potency and stability in a biological context. Specifically, we chose interleukin-17A as a target protein and performed in vitro selection of cyclic peptide aptamers from a library of approximately 10(12) members in the presence of serum. The selected molecules had nanomolar affinity to the target and were stable in serum. Interestingly, we found that a component of the DNA linker that connected the peptide and cDNA may play a pivotal role in target binding.