Cationic Amphiphilic Polyproline Helices (CAPHs): Coupling Antibacterial Activity with Mammalian Cell Penetration

化学系的生命过程化学项目正在资助普渡大学的Jean Chmielewski研究一类被设计为穿过细胞膜的分子。这使得基因或其他所需分子等物质进入人体细胞。然而，如果这些分子与细菌接触，结果可能是细菌死亡，因此这些物质也可能导致新型抗生素。在这项研究中，正在对分子进行改变，以改善这两种活性，并更深入地了解分子的功能方式。这项工作正在产生更广泛的影响，使研究生能够获得专门培训。提高该项目影响力的另一种方式是将其纳入一个外联方案，通过化学和生物学的实践活动向小学生介绍假设和实验的科学方法。在这项研究中，一类分子-阳离子两亲性聚脯氨酸螺旋（CAPH）-已被设计为跨哺乳动物细胞膜易位，并显示抗菌活性正在研究中。拟议研究的目标是探索CAPH内允许有效细胞摄取和抗菌作用的结构特征，同时开发CAPH活性的机制模型。一系列的疏水改性沿着聚脯氨酸螺旋支架正在制备和研究。然后将使用各种方法阐明CAPH的细菌靶标。最终，这项工作将导致更深入地了解如何将诊断工具和探针带入特定细胞。此外，还将开发有机和肽合成、细胞成像和抗菌作用方面的先进技术。

The Chemistry of Life Processes Program in the Division of Chemistry is funding Jean Chmielewski of Purdue University to study a class of molecules that have been designed to cross the cell membrane. This allows substances such as genes or other desired molecules to enter the body's cells. If these molecules come into contact with bacteria, though, the result can be death of the bacteria, so these substances might also lead to new types of antibiotics. In this research, changes to the molecules are being made to improve both of these activities, and also to gain a deeper understanding of the way in which the molecules function. The work is having a broader impact by allowing graduate students to acquire specialized training. Another way the impact of this project is enhanced is through its integration into an outreach program to introduce elementary school students to the scientific method of hypothesis and experimentation through hands-on activities in chemistry and biology. In this research, a class of molecules - cationic amphiphilic polyproline helices (CAPHs) - that have been designed to translocate across mammalian cell membranes and also display antibacterial activity are being investigated. The goals of the proposed research are to probe the structural features within CAPHs that allow for efficient cell uptake and antibacterial action, while developing a mechanistic model for CAPH activity. A range of hydrophobic modifications along the polyproline helical scaffold are being prepared and studied. The bacterial targets of CAPHs will then be elucidated using a variety of methods. Ultimately this work will lead to a deeper understanding of how to bring diagnostic tools and probes into specific cells. In addition, advanced techniques in organic and peptide synthesis, cell imaging and antibacterial action will be developed.