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Networks for recognition of biomolecules: molecular imprinting and micropatterning poly(ethylene glycol)-containing films

机译:识别生物分子的网络:分子印迹和含聚乙二醇的薄膜微图案化

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摘要

Engineering the molecular design of biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. Studies of protein binding domains reveal molecular architectures with specific chemical moieties that provide a framework for selective recognition of target biomolecules in aqueous environment. By matching functionality and positioning of chemical residues, we have been successful in designing biomimetic polymer networks that specifically bind biomolecules in aqueous environments. Our work addresses the preparation, behavior, and dynamics of the three-dimensional structure of biomimetic polymers for selective recognition via non-covalent complexation. In particular, the synthesis and characterization of recognitive gels for the macromolecular recognition of D-glucose is highlighted. Novel copolymer networks containing poly(ethylene glycol) (PEG) and functional monomers such as acrylic acid, 2-hydroxyethyl methacrylate, and acrylamide were synthesized in dimethyl sulfoxide (polar, aprotic solvent) and water (polar, protic solvent) via UV-free radical polymerization. Polymers were characterized by single and competitive equilibrium and kinetic binding studies, single and competitive fluorescent and confocal microscopy studies, dynamic network swelling studies, and ATR-FTIR. Results qualitatively and quantitatively demonstrate effective glucose-binding polymers in aqueous solvent. Owing to the presence of template, the imprinting process resulted in a more macro porous structure as exhibited by dynamic swelling experiments and confocal microscopy. Polymerization kinetic studies suggest that the template molecule has more than a dilution effect on the polymerization, and the effect of the template is related strongly to the rate of propagation. In addition, PEG containing networks were micropatterned to fabricate microstructures, which would be the basis for micro-diagnostic and tissue engineering devices. Utilizing photolithography techniques, polymer micro patterns of a variety of shapes and dimensions have been created on polymer and silicon substrates using UV free-radical polymerizations with strict spatial control. Micropatterns were characterized using optical microscopy, SEM, and profilometry. The processes and analytical techniques presented are applicable to other stimuli-sensitive and recognitive networks for biomolecules, in which hydrogen bonding, hydrophobic, or ionic contributions will direct recognition. Further developments are expected to have direct impact on applications such as analyte controlled and modulated drug and protein delivery, drug and biological elimination, drug targeting, tissue engineering, and micro- or nano-devices. This work is supported by NSF Grant DGE-99-72770.
机译:通过控制识别和特异性来设计生物材料的分子设计是协调和复制复杂的生物和生理过程的第一步。蛋白质结合结构域的研究揭示了具有特定化学部分的分子结构,这些结构为选择性识别水性环境中的目标生物分子提供了框架。通过匹配功能性和化学残基的定位,我们已经成功设计了在水性环境中特异性结合生物分子的仿生聚合物网络。我们的工作解决了仿生聚合物三维结构的制备,行为和动力学问题,以便通过非共价络合进行选择性识别。特别地,突出了用于D-葡萄糖的大分子识别的识别凝胶的合成和表征。在二甲基亚砜(极性,非质子传递溶剂)和水(极性,质子传递溶剂)中,通过无紫外线,合成了包含聚乙二醇(PEG)和丙烯酸,甲基丙烯酸2-羟乙酯和丙烯酰胺等功能性单体的新型共聚物网络。自由基聚合。聚合物的特征在于单一和竞争性平衡与动力学结合研究,单一和竞争性荧光与共聚焦显微镜研究,动态网络膨胀研究以及ATR-FTIR。结果定性和定量地证明了在水性溶剂中有效的葡萄糖结合聚合物。由于模板的存在,压印过程导致了更大的宏观多孔结构,如动态溶胀实验和共聚焦显微镜所显示的。聚合动力学研究表明,模板分子对聚合反应的影响不只是稀释作用,而且模板的作用与繁殖速率密切相关。另外,对包含PEG的网络进行微图案化以制造微结构,这将成为微诊断和组织工程设备的基础。利用光刻技术,使用严格控制空间的UV自由基聚合,已在聚合物和硅基板上创建了各种形状和尺寸的聚合物微图案。使用光学显微镜,SEM和轮廓测定法对微图案进行表征。提出的过程和分析技术适用于其他对生物分子敏感的刺激性和识别性网络,其中氢键,疏水性或离子性贡献将直接识别。预计进一步的发展将直接影响应用,例如分析物控制和调节的药物和蛋白质的输送,药物和生物的消除,靶向药物,组织工程以及微型或纳米设备。 NSF Grant DGE-99-72770支持这项工作。

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