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

有了这个奖项，化学系的生命过程化学项目资助普渡大学的Jean Chmielewski教授研究新设计的细胞穿透化合物的功能。基因、蛋白质、颗粒以及有时小分子进入细胞是被禁止的，因为它们不能充分地穿过细胞膜。 已经设计了一类分子，可以有效地穿过细胞膜进入人体细胞。 这些相同的分子也与细菌细胞相互作用，导致细菌死亡。在这项工作中，对分子进行了改变，以提高这两种活性，并对分子的功能方式有了更深入的了解。这种追求使研究生能够获得有机和肽合成，人体细胞成像和抗菌作用的专业培训。该项目还旨在通过化学多样性倡议增加普渡大学化学系研究生群体的多样性，这是一个三管齐下的计划，旨在成功招募，保留和专业发展代表性不足的少数民族研究生。该研究项目对一类分子，阳离子两亲性聚脯氨酸螺旋（CAPH），其被设计为有效地移位哺乳动物细胞膜并且还显示出有效的抗菌活性。 拟议研究的目标是探索CAPH内的特定结构特征，这些特征允许有效的细胞摄取，亚细胞定位和抗菌作用，同时开发CAPH活性的机制模型。此外，CAPH被利用来改变抗生素（如万古霉素）的特异性以靶向革兰氏阴性细菌。这项研究的信息为哺乳动物和细菌细胞内CAPHs的结构和功能提供了更深入的机制见解。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.