Molecular recognition binding sites that specifically identify a target molecule are essential for life science research, clinical diagnoses, and therapeutic development. Corona phase molecular recognition is a technique introduced to generate synthetic recognition at the surface of a nanoparticle corona, but it remains an important question whether such entities can achieve the specificity of natural enzymes and receptors. In this work, we generate and screen a library of 24 amphiphilic polymers, preselected for molecular recognition and based on functional monomers including methacrylic acid, acrylic acid, and styrene, iterating upon a poly(methacrylic acid-co-styrene) motif. When complexed to a single-walled carbon nanotube, some of the resulting corona phases demonstrate binding specificity remarkably similar to that of phosphodiesterase type 5 (PDE5), an enzyme that catalyzes the hydrolysis of secondary messenger. The corona phase binds selectively to a PDE5 inhibitor, Vardenafil, as well as its molecular variant, but not to other potential off-target inhibitors. Our work herein examines the specificity and sensitivity of polymer “mutations” to the corona phase, as well as direct competitions with the native binding PDE5. Using structure perturbation, corona surface characterization, and molecular dynamics simulations, we show that the molecular recognition is associated with the unique three-dimensional configuration of the corona phase formed at the nanotube surface. This work conclusively shows that corona phase molecular recognition can mimic key aspects of biological recognition sites and drug targets, opening up possibilities for pharmaceutical and biological applications.

特异性识别靶分子的分子识别结合位点对于生命科学研究，临床诊断和治疗开发至关重要。电晕相分子识别是一种引入的技术，可在纳米粒子电晕的表面上产生合成识别，但是，此类实体是否可以实现天然酶和受体的特异性仍然是一个重要的问题。在这项工作中，我们生成并筛选了24种两亲聚合物的库，这些库预先选择用于分子识别，并基于包括甲基丙烯酸，丙烯酸和苯乙烯在内的功能性单体进行迭代，以迭代聚（甲基丙烯酸-共苯乙烯）基序。当与单壁碳纳米管复合时，一些产生的电晕相显示出与5型磷酸二酯酶（PDE5）相似的结合特异性，该酶催化次级信使的水解。电晕相选择性结合PDE5抑制剂Vardenafil及其分子变体，但不结合其他潜在的脱靶抑制剂。我们在本文中的工作研究了聚合物“突变”对电晕相的特异性和敏感性，以及与天然结合PDE5的直接竞争。使用结构扰动，电晕表面表征和分子动力学模拟，我们表明分子识别与纳米管表面形成的电晕相的独特三维构型有关。