Control of beta-Sheet Self-Assembly through Chemical Crosslinks

有了这个奖项，生命过程的化学计划正在支持加州大学欧文分校化学系的James Nowick教授的研究，以设计，合成和研究大环模型系统，以更好地了解肽组装和聚集。虽然结构生物学家已经广泛研究了处于折叠状态的蛋白质，但越来越清楚的是，它们的错误折叠和聚集状态在生物学中也至关重要。化学模型系统为更好地研究这些复杂状态提供了理想的方法。这里正在开发的模型系统将允许边到边的氢键和面对面的疏水相互作用的调查，特别是在β-片层样组件。 由于模型系统是以受控方式相互作用的大环化合物，因此有可能使用本文开发的系统来控制和调节肽基二级结构并最终调节蛋白质聚集。更好地理解β-折叠样结构中的分子组装和聚集可能在化学和生物学中产生广泛的科学影响，远远超出本项目。 该项目的教育部分包括生物有机和肽模型化学的研究生和本科生的跨学科培训。 此外，PI和他的学生将继续努力通过“UCI化学推广计划”激发K-12水平的化学和科学兴趣。“PI发起了这个项目，在过去的二十年里，它已经覆盖了数千名K-12学生。

With this award, the Chemistry of Life Processes program is supporting the research of Professor James Nowick of the Department of Chemistry at the University of California, Irvine to design, synthesize and study macrocyclic model systems to better understand peptide assembly and aggregation. While proteins in their folded states have been widely studied by structural biologists, it is becoming increasingly clear that their poorly understood misfolded and aggregated states are also of critical importance in biology. Chemical model systems provide an ideal way to better study these complex states. The model systems being developed here will allow the investigation of edge-to-edge hydrogen bonding and face-to-face hydrophobic interactions, particularly in beta-sheet-like assemblies. Because the model systems are macrocycles that interact in a controlled fashion, it may be possible to use the systems developed here to control and modulate peptidyl secondary structure and eventually protein aggregation.A better understanding of molecular assembly and aggregation in beta-sheet-like structures could have broad scientific impact, well beyond this project, in chemistry and biology. Educational components of this project include the cross-disciplinary training of graduate and undergraduate students in bioorganic and peptide model chemistry. In addition, the PI and his students will continue in their efforts to spark interest in chemistry and science at the K-12 level through the "UCI Chemistry Outreach Program." The PI initiated this program and it has now reached thousands of K-12 students over the past two decades.