Develop Conditionaly Charged Residues for the Design of Peptide Channels

通过这一奖项，生命过程化学项目支持波士顿学院化学系高建民教授的研究。高教授将开发和测试一类新的非天然氨基酸，这种氨基酸在与脂膜相互作用时会改变其电离状态。这些氨基酸被称为条件带电残基(CCRs)，因为它们在水溶液中是带正电荷的，但当放置在非极性环境中时，如脂膜，则是中性的。可望在生物有机和药物化学中有广泛的应用前景。在这个项目中，合成的CCRs将作为一个模型系统并入到具有良好特性的通道形成肽Granicidin A中。高教授将研究多肽的结构决定因素，使它们能够有效地折叠到跨膜通道中。该项目的更广泛的影响包括开发一套广泛适用的非蛋白原性氨基酸用于化学生物学，以及它们在促进我们对肽-膜相互作用的理解方面的部署。同样重要的是对研究生和本科生进行跨学科研究的教育和培训。培训计划包括通过PI与罗克斯伯里社区学院(RCC)共同发起的实习生计划的外展部分。

With this award, the Chemistry of Life Processes program is supporting the research of Professor Jianmin Gao of the Department of Chemistry at Boston College. Professor Gao will develop and test a novel class of unnatural amino acids that change their ionization states upon interacting with lipid membranes. These amino acids are designated as "Conditionally Charged Residues" (CCRs) as they are designed to be positively charged in aqueous solution, but neutral when placed in a nonpolar environment such as a lipid membrane. It is expected that such CCRs will have broad application in bioorganic and medicinal chemistry. In this project, the synthesized CCRs are to be incorporated into the well characterized channel forming peptide, gramicidin A, as a model system. Professor Gao will examine the structural determinants of peptides that enable their efficient folding into transmembrane channels. The Broader Impacts of this project include the development of a set of widely applicable non-proteinogenic amino acids for use in chemical biology and their deployment toward advancing our understanding of peptide-membrane interactions. Of equal importance is the education and training of graduate and undergraduate students in interdisciplinary research. The training program includes an outreach component through the intern program that the PI has initiated with Roxbury Community College (RCC).