SYNTHETIC ANTIBODIES BY MONOMOLECULAR POLYMER IMPRINTING

该提案描述了一项主要的新倡议，即通过“单分子”印迹工艺开发合成抗体。分子印迹聚合物（MIPs）是一种成熟的材料，因其影响生物技术和生物医学的非凡潜力而得到广泛认可。这些材料是通过在模板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MIPs实现商业应用。这些限制主要是结合位点的异质性，缓慢的质量传递，不溶性，难以定量地去除模板，以及大多数MEN不能在水中发挥作用。提议的努力将开发一种“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一个包含单个结合位点的纳米结构，该结合位点在其功能基团阵列上与模板分子（抗原）具有形状选择性和互补性。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。为了进行比较，我们直接借鉴了聚合物印迹的几种方法。最初要研究的聚合物在结构上将是树枝状的。该方法的一个主要优点是，虽然会产生多种化合物（多克隆方法），但可以分离出最有效的化合物。此外，这些“合成抗体”有望表现出快速的结合动力学，易于化学修饰（例如，在一系列介质中的溶解度，附着在表面上），并且具有易于移动的模板。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，并且结合强度和选择性可以调整。医疗诊断方面的应用最有可能是这项技术的早期成果。

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.