Wang Yongwei, Zhao Ting, Dai Peng, Jiang Nan, Li Fei
Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China.
Chemphyschem. 2016 Mar 16;17(6):893-901. doi: 10.1002/cphc.201500941. Epub 2016 Jan 20.
Molecularly imprinted polymers (MIPs) are employed to screen nNOS-PSD-95 (neuronal nitric oxide synthase post-synaptic density protein-95) interruptions. 5-(3,5-Dichloro-2-hydroxybenzylamino)-2-hydroxybenzoic acid (ZL006; a potential drug candidate for the treatment of stroke, depression, and pain) is employed as a template. Four kinds of functional monomers (2-VP: 2-vinylpyridine; 4-VP: 4-vinylpyridine; MMA: methyl methacrylate; and MAAM: methacrylamide) are designed, and their complexation with ZL006 in various solvents (methanol, acetonitrile, toluene, chloroform) is investigated by molecular dynamics simulations and quantum mechanics calculations. Both 4-VP and MAAM have stronger interactions with ZL006 than those of 2-VP and MMA. The appropriate ratio of monomer to template is 3:1. Intermolecular hydrogen bonds play a dominant role in monomer-template complexation. Ideal solvents are toluene and chloroform, and the solvation effect on monomer-template complexation is revealed. Both molecular modeling and adsorption experiments demonstrate that as-synthesized ZL006-MIP with 4-VP as a monomer has better selectivity than that employing MAAM to screen for nNOS-PSD-95 interruptions.
分子印迹聚合物（MIPs）被用于筛选神经元型一氧化氮合酶-突触后致密蛋白95（nNOS-PSD-95）的干扰情况。5-（3,5-二氯-2-羟基苄氨基）-2-羟基苯甲酸（ZL006；一种治疗中风、抑郁症和疼痛的潜在候选药物）被用作模板。设计了四种功能单体（2-乙烯基吡啶：2-VP；4-乙烯基吡啶：4-VP；甲基丙烯酸甲酯：MMA；和甲基丙烯酰胺：MAAM），并通过分子动力学模拟和量子力学计算研究了它们在各种溶剂（甲醇、乙腈、甲苯、氯仿）中与ZL006的络合情况。4-VP和MAAM与ZL006的相互作用比2-VP和MMA更强。单体与模板的合适比例为3:1。分子间氢键在单体-模板络合中起主导作用。理想的溶剂是甲苯和氯仿，并揭示了溶剂化对单体-模板络合的影响。分子建模和吸附实验均表明，以4-VP作为单体合成的ZL006-MIP在筛选nNOS-PSD-95干扰方面比使用MAAM的具有更好的选择性。
