Molecular Recognition by Protein Kinases

本研究的重点是合成多聚L-脯氨酸II型多肽模拟物，并将其用作蛋白激酶底物，目的是更好地确定影响蛋白激酶底物特异性的一级和二级结构参数。PPII模拟物的构建将利用构象控制元件，这些元件定义了一个全脯氨酸PPII螺旋。这将包括合成在Pro主干上具有非Pro侧链的修饰的Pro类似物，并从这些修饰的Pro生成寡肽。通过这一新奖项，有机和高分子化学项目将支持佛蒙特州大学化学系何塞·S·马达伦戈蒂亚博士的研究。Madalengoitia教授将专注于探索这一假设，即至少有一些蛋白激酶在PPII构象中或在类似于这种几何结构的延伸构象中磷酸化多肽链。随着该项目的成功，将在当前生物学的一个重要领域产生重大影响。

The focus of this research is the synthesis of poly-l-proline type II peptide mimics and the use of these mimics as kinase substrates with the goal of better defining the primary and secondary structure parameters which contribute to the substrate specificity of protein kinases. Construction of PPII mimics will utilize conformational control elements which define an all-proline PPII helix. This will involve the synthesis of modified proline analogs possessing the non-prolyl side chains on the proline backbone and the generation of oligopeptides from these modified prolines. With this new award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Jose S. Madalengoitia of the Department of Chemistry at the University of Vermont. Professor Madalengoitia will focus his work on probing the hypothesis that at least some protein kinases phosphorylate peptide strands in the PPII conformation, or in extended conformations resembling this geometry. High impact in an important area of current biology will occur with the success of this project.