SYNTHETIC ANTIBODIES BY MONOMOLECULAR POLYMER IMPRINTING

这项提议描述了一项重大的新倡议，即通过“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。这些限制的主要原因是结合部位的异质性、缓慢的传质、不溶性、难以定量去除模板以及大多数人无法在水中发挥作用。这项拟议的工作将开发一种“成型”协议，在该协议中，共价连接到模板上的单个聚合物结构将被广泛地交联。模板的共价裂解将留下包含单个结合位置的纳米结构，该结合位置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。在该项目的早期阶段要研究的模板包括碳水化合物、氨基酸、多肽和药物分子。有几种方法直接从聚合物印迹中借用来进行比较。最初要研究的聚合物将是树枝状结构。这种方法的一个主要优点是，尽管会产生多个化合物(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”应该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性，附着在表面上)，并且具有容易移除的模板。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。

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.