Beta-Peptide Inhibitors of Protein-Protein Interactions

描述(由申请人提供)：蛋白质-蛋白质相互作用在细胞功能中非常重要，因此是药物化学的靶标。传统的基于小分子的药物设计在开发某些相互作用的拮抗剂方面被证明是无效的，而大分子方法正在找到越来越有用的方法。人表皮生长因子受体(EGFR)是一种膜结合的细胞表面受体，其功能障碍与多种癌症有关。我们建议通过模拟参与受体二聚化的蛋白质表面来识别能够调节EGFR功能的β-肽折叠分子。该项目将使我们能够探索β-肽支架作为天然蛋白质表面模拟物的范围和局限性，并可能导致新的抗癌疗法的开发。

DESCRIPTION (provided by applicant): Protein-protein interactions are of great importance in cell function and, consequently, as targets for medicinal chemistry. Where traditional small-molecule based drug design has proven ineffective in the development of antagonists of certain interactions, macromolecular approaches are finding increasing utility. Human epidermal growth factor receptor (EGFR) is a membrane bound cell surface receptor the malfunction of which is linked to a number of cancers. We propose to identify beta-peptide foldamers capable of modulating EGFR function by mimicking protein surfaces involved in receptor dimerization. This project will allow us to explore the scope and limitations of beta-peptide scaffolds as mimics of natural protein surfaces and could lead to the development of new anticancer therapeutics.