Targeting protein-protein interactions using chemcial approaches

有了这个奖项，生命过程计划的化学是支持教授Hyun-Suk林，生物化学和分子生物学系在印第安纳州医学院开发蛋白质-蛋白质相互作用（PPI）的新调节剂。这种PPI调节剂在当今的化学生物学和药物化学中有很高的需求。 这里所采取的方法涉及构象约束的芳基桥接的环状/双环类肽轴承螺旋模拟片段的设计，合成和评价。设计特征包括相对大的尺寸、高的结构多样性和增加的构象刚性，所有特征预期促进与大的和不连续的蛋白质界面的结合。与常规肽相比，这些环状类肽支架预期显示出改善的水溶性、优异的细胞渗透性并且易于合成。该项目将使研究生和博士后研究员接触到具有显着合成成分的多学科化学生物学环境。该项目还将通过生命健康科学实习（LHSI）计划为印第安纳州大学-印第安纳波利斯普渡大学（IUPUI）的本科生提供培训机会。此外，由IUPUI研究生办公室支持的代表性不足的少数民族学生将参与其中。林教授还将参加由IUPUI领导的“分布式药物发现”（D3）计划，将本科教育纳入寻找被忽视疾病的药物线索。

With this award, the Chemistry of Life Processes Program is supporting Professor Hyun-Suk Lim, of the Department of Biochemistry and Molecular Biology at Indiana University School of Medicine to develop new modulators of protein-protein interactions (PPIs). Such PPI modulators are in high demand in chemical biology and medicinal chemistry today. The approach taken here involves the design, synthesis and evaluation of conformationally constrained aryl-bridged cyclic/bicyclic peptoids bearing helix-mimetic segments. Design features include relatively large size, a high structural diversity, and increased conformational rigidity, all features expected to promote binding to large and non-contiguous protein interfaces Compared to conventional peptides, these cyclic peptoid scaffolds are expected to display improved aqueous solubility, excellent cell permeability and be easily accessed synthetically. This project will exposed graduate students and postdoctoral fellows to multidisciplinary chemical biology environment with a notable synthetic component. The project will also provide training opportunity to undergraduate students at Indiana University - Purdue University at Indianapolis (IUPUI) through the Life Health Science Internship (LHSI) program. In addition, underrepresented minority students supported by IUPUI Graduate Office will be involved. Professor Lim will also participate in "Distributed Drug Discovery" (D3) program led by IUPUI to incorporate undergraduate education into the search for drug leads for neglected diseases.