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

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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.