Cationic Amphiphilic Polyproline Helices for Cell Penetration

Purdue University, West Lafayette IN

Investigators

Abstract

The Chemistry of Life Processes program supports Professor Jean Chmielewski at the Purdue University in developing cationic amphiphilic polyproline helices for penetrating selective cells. The passive uptake of genes, polypeptides, particles and, at times, small molecules into cells is prohibited due to their inability to adequately cross the membrane bilayer. The PI's group has designed a class of molecules, cationic amphiphilic polyproline helices (CAPHs), that have been shown to effectively cross the cell membrane and enter certain cells selectively. The goals of the proposed research seek to explore specific structural features within CAPHs that allow for efficient cell uptake using the tools of synthetic chemistry and membrane biochemistry (model and cellular), and to harness the remarkable cell penetrating characteristics of CAPHs for the delivery of cargo within the cell. With these goals in mind, the specific questions that will be addressed include: (1) What features of CAPHs may be modified to promote membrane penetration and specificity? (2) What is the mechanism used by CAPHs to interact with the lipid bilayer and to cross cellular membranes? (3) What small molecule fluorophores may be imported into cells through non-covalent association with oligomeric CAPHs? The ability of highly cationic molecules to cross the hydrophobic cell membrane is unusually evocative and would have a broad impact on many areas of science, including nanotechnology, gene therapy, drug delivery, and basic membrane biochemistry. As the PI continues to advance the knowledge base of cationic amphiphile/membrane interactions, she will reach out to other scientific disciplines by writing comprehensive reviews of the area and will participate in more public forums to share results and perspectives with non-scientists. This area of research--combining chemistry and biology--also would have broad impact as the foundation for exposure to interdisciplinary aspects of science to younger students. With this in mind, the PI has developed an outreach program targeting high school students and their teachers. It is the goal of these outreach efforts that a significant group of Indiana high school students and teachers will learn to appreciate the overlap of modern scientific disciplines through true hands-on exposure. These studies are directed at the development of shuttles with which molecules can enter cells. Ultimately this work will lead to a deeper understanding of how to bring therapies, diagnostic tools and probes into specific cells.