Synthetic Antibodies by Monomolecular Imprinting

描述(由申请人提供)：我们建议继续我们的新倡议，通过“单分子”印迹过程开发合成抗体。分子印迹聚合物(MIP)是公认的具有影响生物技术和生物医学的非凡潜力的材料。这些材料是通过在模板的存在下进行聚合反应而形成的。然而，一些尚未克服的限制阻碍了MIP实现商业应用。这些限制包括：结合位置的异质性，缓慢的传质，不溶性，难以定量地去除模板，以及大多数分子印迹聚合物无法在水中发挥作用。这项拟议的工作将继续开发一种“成型”方案，在该方案中，单一聚合物结构将围绕单一模板进行广泛的交联化。模板的移除留下包含单个结合部位的纳米结构，该结合部位在其功能基团阵列中对模板分子(抗原)具有形状选择性和互补性。 本预算期间的重点将是开发产生更多刚性印记的新建筑。这将涉及定向闭环易位反应，该反应增加树枝状或星形聚合物结构内的交联度，并有利于交联度更接近模板。还将努力在高度刚性的结构中建立通往结合部位的工程通道。在该项目的早期阶段要研究的模板包括碳水化合物、神经递质、多肽和药物分子。聚合物结构、溶剂、类型和交联度的无限修改使这种方法非常有可能成功，并且结合强度和选择性可以调节。在医疗诊断中的应用最有可能是这项技术的早期回报。

DESCRIPTION (provided by applicant): We propose to continue our new initiative to develop synthetic antibodies by a "mono-molecular" imprinting process. Molecular imprinted polymers (MIPs) are well-established materials widely acknowledged for their extraordinary potential to impact biotechnology and biomedicine. These materials are formed by carrying out a polymerization reaction in the presence of a template. However, several limitations not yet overcome, have prevented MIPs from achieving commercial applicability. These limitations include: binding site heterogeneity, slow mass transfer, insolubility, difficulty in quantitatively removing the template, and an inability of most MIPs to function in water. The proposed effort will continue development of a "molding" protocol in which a single polymeric structure will be extensively cross-linked around a single template. Removal of the template leaves a nanostructure containing a single binding site that is both shape-selective and complementary in its functional group array to the template molecule (antigen). Emphasis in this budget period will be on developing new architectures that produce more rigid imprints. This will involve directed ring closing metathesis reactions that increase cross-links within the dendritic or star polymer structure and favor cross-linking closer to the template. Efforts will also be directed toward engineering channels to the binding site in highly rigid structures. The templates to be investigated in this early phase of the project include carbohydrates, neurotransmitters, peptides, and drug molecules. Infinite modifications in the polymer structure, solvent, type and degree of cross-linking makes it very likely that this approach will be successful, and that the binding strength and selectivity can be tuned. Applications in medical diagnostics are the most likely early pay-off for this technology.