SYNTHETIC ANTIBODIES BY MONOMOLECULAR POLYMER IMPRINTING

该提案描述了通过“单分子”印迹过程开发合成抗体的主要新倡议。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。这些限制中的主要是结合位点异质性、缓慢的质量传递、不溶性、难以定量去除模板以及大多数MEN不能在水中起作用。拟议的努力将开发一个“成型”协议，其中一个单一的聚合物结构，共价连接到一个模板，将广泛交联。模板的共价切割将留下含有单个结合位点的纳米结构，该结合位点既是形状选择性的，又在其官能团阵列中与模板分子（抗原）互补。在这个项目的早期阶段要研究的模板包括碳水化合物、氨基酸、肽和药物分子。为了比较的目的，直接从聚合物印迹中借用了几种方法。待研究的初始聚合物将是树枝状结构。这种方法的主要优点是，尽管将产生多种化合物（多克隆方法），但可以分离最有效的化合物。此外，预期这些“合成抗体”显示快速结合动力学，容易化学修饰（例如，在一系列介质中的溶解度，附着于表面），并具有容易去除的模板。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。

This proposal describes a major 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. Principal among these limitations is binding site heterogeneity, slow mass transfer, insolubility, difficulty in quantitatively removing the template, and an inability of most MEN to function in water. The proposed effort will develop a "molding" protocol in which a single polymeric structure, covalently connected to a template, will be extensively cross-linked. Covalent cleavage of the template will leave a nanostructure containing a single binding site that is both shape-- selective and complementary in its functional group array to the template molecule (antigen). The templates to be investigated in this early phase of the project include carbohydrates, amino acids, peptides, and drug molecules. Several approaches are borrowed directly from polymer imprinting for comparison purposes. The initial polymers to be studied will be dendritic in structure. A major advantage of this approach is that although multiple compounds will be produced (polyclonal approach) one might separate the most efficacious compounds. Furthermore, these "synthetic antibodies" are expected to show rapid binding kinetics, be easily modified chemically (e.g., solubility in a range of media, attachment to surfaces), and to have readily removable templates. 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.