Tyrosine phosphorylation (pTyr), many of which occurred on localized multiple sites, initiates cellular signaling, governs cellular functions, and its dysregulation is implicated in many diseases, especially cancers. pTyr-specific sensing is of great significance for understanding disease states and developing targeted anti-cancer drugs, however, is very challenging due to the slight difference from serine (pSer) or threonine phosphorylation (pThr). Here we present a polyethyleneimine-g-phenylguanidine (PEI-PG)-modified nanochannels that can address the challenge. Rich guanidinium groups enabled PEI-PG to form multiple interactions with phosphorylated residues, especially pTyr residue, which triggered the conformational change of PEI-PG. By taking advantage of "OFF-ON" change of ion flux arising from conformational shrinkage of the grafted PEI-PG, the nanochannels could distinguish phosphorylated peptide (PP) from non-modified peptide, recognize PPs with pSer, pThr or pTyr residue and PPs with different number of identical residues, and importantly could sense pTyr peptides in a bio-sample. Benefiting from the strong interaction between guanidinium group and pTyr side-chain, the specific sensing of pTyr peptide was achieved by performing simple logic operation based on PEI-PG-modified nanochannels when Ca2+ was introduced as an interferent. The excellent pTyr sensing capacity make the nanochannels available for real-time monitoring of pTyr process by c-Abl kinase on a peptide substrate, even in a complicated condition, and the proof-of-concept study of monitoring kinase activity demonstrates its potential in kinase inhibitor screening.

中文翻译：

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用于检测酪氨酸磷酸化的功能性纳米通道

酪氨酸磷酸化 (pTyr)，其中许多发生在多个局部部位，启动细胞信号传导，控制细胞功能，其失调与许多疾病有关，尤其是癌症。pTyr 特异性传感对于了解疾病状态和开发靶向抗癌药物具有重要意义，但由于与丝氨酸 (pSer) 或苏氨酸磷酸化 (pThr) 略有不同，因此非常具有挑战性。在这里，我们提出了一种可以应对挑战的聚乙烯亚胺-g-苯基胍（PEI-PG）修饰的纳米通道。丰富的胍基团使 PEI-PG 能够与磷酸化残基，尤其是 pTyr 残基形成多重相互作用，从而引发 PEI-PG 的构象变化。通过利用“OFF-ON” 由于接枝 PEI-PG 的构象收缩引起离子通量的变化，纳米通道可以区分磷酸化肽 (PP) 和未修饰的肽，识别具有 pSer、pThr 或 pTyr 残基的 PP 以及具有不同数量的相同残基的 PP，重要的是可以感应生物样品中的 pTyr 肽。受益于胍基团与 pTyr 侧链之间的强相互作用，当引入 Ca2+ 作为干扰物时，通过基于 PEI-PG 修饰的纳米通道进行简单的逻辑运算，实现了 pTyr 肽的特异性传感。出色的 pTyr 传感能力使纳米通道可用于通过肽底物上的 c-Abl 激酶实时监测 pTyr 过程，即使在复杂的条件下，