Synthetic Antibodies by Monomolecular Imprinting

描述（由申请人提供）：我们建议继续我们的新举措，通过“单分子”印迹过程开发合成抗体。分子印迹聚合物（MIPs）是一种成熟的材料，因其对生物技术和生物医学的巨大影响而被广泛认可。这些材料通过在模板存在下进行聚合反应而形成。然而，一些尚未克服的限制已经阻止了MIP实现商业应用。这些限制包括：结合位点不均一性、缓慢的质量传递、不溶性、难以定量除去模板以及大多数MIP不能在水中起作用。拟议的努力将继续发展一个“成型”协议，其中一个单一的聚合物结构将广泛交联周围的一个单一的模板。模板的去除留下含有单一结合位点的纳米结构，所述单一结合位点在其官能团阵列中与模板分子（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新的架构，以产生更严格的印记。这将涉及定向闭环复分解反应，其增加树枝状或星星聚合物结构内的交联并有利于更靠近模板的交联。努力也将针对工程通道的结合位点在高度刚性的结构。该项目早期阶段要研究的模板包括碳水化合物、神经递质、肽和药物分子。聚合物结构、溶剂、交联类型和程度的无限修改使得这种方法很可能成功，并且可以调整结合强度和选择性。医疗诊断应用是这项技术最有可能的早期回报。

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.