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

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Jean Chmielewski from Purdue University to investigate how newly designed cell penetrating compounds function. The entry of genes, proteins, particles and, at times, small molecules into cells is prohibited due to their inability to adequately cross the membrane of cells. A class of molecules has been designed that effectively cross the cell membrane and enter human cells. These same molecules also interact with bacterial cells leading to the death of the bacteria. In this work, changes to the molecules are made to improve both of these activities, and also to gain a deeper understanding of the way in which the molecules function. This pursuit allows graduate students to acquire specialized training in organic and peptide synthesis, human cell imaging and antibacterial action. This project also seeks to increase the diversity of the graduate student population in the chemistry department at Purdue University through the Chemistry Diversity Initiative, a three-pronged program for the successful recruitment, retention and professional development of underrepresented minority graduate students.This research project undertakes mechanistic studies of a class of molecules, cationic amphiphilic polyproline helices (CAPHs), that are designed to effectively translocate mammalian cell membranes and also display potent antibacterial activity. The goals of the proposed research are to probe the specific structural features within CAPHs that allow for efficient cell uptake, subcellular localization and antibacterial action, while developing a mechanistic model for CAPH activity. Additionally, CAPHs are harnessed to alter the specificity of antibiotics, such as vancomycin, to target Gram negative bacteria. Information from this study provides a deeper mechanistic insight into the structure and function of CAPHs within mammalian and bacterial cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.