PPII Mimics as Probes of the Active Site Occupancy Requirements of Protein Kinases

本研究的重点是合成模拟聚l -脯氨酸II型（PPII）构象的化合物。该策略包括制备脯氨酸模板氨基酸（PTAAs），当它们在溶液中偶联时，顺序填充PPII构象。然后，PPII模拟物将作为合成针对至少一组蛋白激酶的抑制剂的一般支架。通过这个奖项，有机和大分子化学项目支持佛蒙特州立农业学院化学系Jose S. Madalengoitia博士的研究和教育活动。Madalengoitia教授将专注于开发蛋白激酶抑制剂的制备方法。这些抑制剂对解开复杂的信号级联很有用。这个项目应该对医学科学产生更广泛的影响，因为异常的蛋白激酶活性与许多疾病状态有关。此外，该项目将为本科生和研究生提供多样化的培训。

The focus of this research involves the synthesis of compounds that mimic the poly-L-proline type II (PPII) conformation. The strategy involves the preparation of proline templated amino acids (PTAAs) that when coupled sequentially populate the PPII conformation in solution. The PPII mimics will then serve as a general scaffold for the synthesis of inhibitors that target at least a subset of protein kinases.With this award, the Organic and Macromolecular Chemistry Program is supporting the research and educational activities of Dr. Jose S. Madalengoitia in the Department of Chemistry at the University of Vermont & State Agricultural College. Professor Madalengoitia will focus his work on developing methods for preparation of protein kinase inhibitors. These inhibitors are useful for unraveling complex signal cascades. This project should have broader impacts for medical science since aberrant protein kinase activity has been linked to many disease states. Also, the project will offer diverse training to undergraduates as well as graduate students.