Molecularly Imprinted Polymers for the selective trageting of phosphotyrosine-containing proteins and peptides

在这个项目中，我们的目标是实现基于1纳米和100纳米长度尺度的结构控制的新一代分层印迹材料。在1 nm长度范围内的控制是通过使用宿主单体来实现的，该宿主单体旨在结合到修饰氨基酸的给定氨基酸的侧链上，这里是磷酸化的氨基酸。通过使用非蛋白质替代物作为模板，实现了在10 nm长度范围内的控制，从而允许制备蛋白质结合部位的大小互补多肽。我们预计，结合这些方法将导致强大的受体能够捕获特定大小的多肽或蛋白质靶标，但具有明确的替代模式。在蛋白质组学领域，这些相可以起到类选择性亲和相的作用，用于分离和浓缩低丰度修饰蛋白。磷酸化是一种具有深远生物学意义的修饰。磷酸化蛋白在细胞间信号转导过程中起着至关重要的作用，其分析是蛋白质组学研究的重要组成部分。通过上述亚结构方法制备的分子印迹聚合物的应用可能带来一种利用分子印迹聚合物处理不稳定生物分子的新概念，并为基于亲和力的蛋白质浓缩开辟了一条广泛的定制材料的道路，从而代表着靶向蛋白质组学领域的重大进展。

In this project, we aim at the realisation of new generations of hierachically imprinted materials based on structural control at both the 1 and 100 nm length scales. Control at the 1 nm length scale is achieved by using host monomers designed to bind to the side chain of given amino acids of modified amino acids, here phosphorylated ones. Control at the 10 nm length scale is achieved by using non-proteinaceous protein surrogates as templates, thus allowing the preparation of size complementary peptide of protein binding sites. We anticipate that combining these approaches will result in robust receptors capable of capturing peptide or protein targets of a certain size but with a defined substitution of substitution pattern. In the area of proteomics, such phases could play the role of class selective affinity phases for fractionation and enrichment of low abundant modified proteins. Phosphorylation is a modification of profound biological importance. Phosphorylated proteins are of critical importance in intercellular signal transduction processes and their analyses forms an important part of proteomics research. The application of MIPs prepared via the above substructure approaches may lead to a new concept in addressing labile biomolecules with MIPs and open the way to a wide range of tailored materials for affinity-based enrichment of proteins, thus representing a major advance in the field of targeted proteomics.