The high expression of Spermidine/spermine N¹-acetyltransferase (SSAT-1) is an important indicator in early cancer diagnosis. Here, we developed a nanopore-based methodology with γ-cyclodextrin as an adaptor to detect and quantify acetylamantadine, the specific SSAT-1-catalyzed product from amantadine, to accordingly reflect the activity of SSAT-1. We employ γ-cyclodextrin and report that amantadine cannot cause any secondary signals in γ-cyclodextrin-assisted α-HL nanopore, while its acetylation product, acetylamantadine, does. This allows γ-cyclodextrin to practically detect acetylamantadine in the interference of excessive amantadine, superior to the previously reported β-cyclodextrin. The quantification of acetylamantadine was not interfered with even a 50-fold amantadine and displayed no interference in artificial urine sample analysis, which indicates the good feasibility of this nanopore-based methodology in painless cancer prediagnosis. In addition, the discrimination mechanism is also explored by 2-D nuclear magnetic resonance (NMR) and nanopore experiments with a series of adamantane derivatives with different hydrophilic and hydrophobic groups. We found that both the hydrophobic region matching effect and hydrophilic interactions play a synergistic effect in forming a host–guest complex to further generate the characteristic signals, which may provide insights for the subsequent design and study of drug-cyclodextrin complexes.

中文翻译：

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γ-环糊精辅助 α-HL 纳米孔测定乙酰金刚烷胺用于潜在癌症预诊断


精胺/精胺N ¹ -乙酰转移酶（SSAT-1）的高表达是早期癌症诊断的重要指标。在这里，我们开发了一种基于纳米孔的方法，以γ-环糊精为适配器来检测和定量乙酰金刚烷胺（金刚烷胺的特定SSAT-1催化产物），从而相应地反映SSAT-1的活性。我们使用γ-环糊精并报告金刚烷胺不能在γ-环糊精辅助的α-HL纳米孔中引起任何次级信号，而其乙酰化产物乙酰金刚烷胺却可以。这使得γ-环糊精能够在过量金刚烷胺的干扰下实际检测乙酰金刚烷胺，优于先前报道的β-环糊精。乙酰金刚烷胺的定量即使是50倍的金刚烷胺也不会受到干扰，并且在人工尿液样本分析中也没有表现出干扰，这表明这种基于纳米孔的方法在无痛癌症预诊断中具有良好的可行性。此外，还通过二维核磁共振（NMR）和纳米孔实验探索了一系列具有不同亲水和疏水基团的金刚烷衍生物的区分机制。我们发现疏水区域匹配效应和亲水相互作用在形成主客体复合物中发挥协同作用，进一步产生特征信号，这可能为药物-环糊精复合物的后续设计和研究提供见解。