title: Employment of Molecularly Imprinted Polymers to High-Throughput Screen nNOS-PSD-95 Interruptions: Structure and Dynamics Investigations on Monomer-Template Complexation.
abstract: 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.
authors.affiliation: Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Dai
authors.affiliation: Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China. jiangnan@njmu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Collaborative Innovation Center for Cardiovascular Disease, Translational Medicine of Jiangsu, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, P. R. China. kldlf@njmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000636:Aminosalicylic Acids / Q000737:chemistry*; D001596:Benzylamines / Q000737:chemistry*; D057166:High-Throughput Screening Assays; D006860:Hydrogen Bonding; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008768:Methylmethacrylates / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D054802:Molecular Imprinting; D052248:Nitric Oxide Synthase Type I / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry*; D011789:Quantum Theory; D012997:Solvents
chemical_list: D000178:Acrylamides; D000636:Aminosalicylic Acids; D001596:Benzylamines; D047908:Intracellular Signaling Peptides and Proteins; D008768:Methylmethacrylates; D011725:Pyridines; D012997:Solvents; C000607694:ZL006 compound; C030953:2-vinylpyridine; D052248:Nitric Oxide Synthase Type I; C029351:4-vinylpyridine; C045985:methacrylamide
keywords: biological activity; molecular dynamics; molecularly imprinted polymers; solvent effects; template synthesis