CAREER: Design of Self-Assembled Stimulus Responsive Peptide Complexes

本研究计划探讨自组装刺激反应肽复合物的设计。α螺旋线圈由两条或两条以上的螺旋链组成，缠绕成一个超螺旋，它们通过核心疏水和表面亲水性氨基酸侧链之间的相互作用相互结合。通过在线圈环境中引入非天然氨基酸，这些研究将产生更多不同的序列，从而允许设计适合下一代肽水凝胶的复合物。通过将适当的行为设计成分离的肽复合物，本研究解决了对生理刺激（pH值、温度、盐梯度）做出反应的“智能”材料的设计。将设立一个正式的化学生物学课程，招收和培训本科生和研究生，学习化学生物学的基础知识和应用知识，弥合化学和生物学之间的差距。在有机和大分子化学项目的CAREER奖的支持下，科罗拉多州立大学化学系的Alan Kennan教授正在进行与设计蛋白质聚集相关的基础研究。通过开发有关导致蛋白质采用特定结构的因素的信息，凯南教授设计了蛋白质的组装，这些蛋白质有望在对环境的反应中表现出不同寻常的变化。这些研究可能会导致“智能”材料的发展，这些材料可以对酸度、温度和盐浓度等生理刺激做出反应。凯南教授将担任化学生物学新项目的主任，为招收和培训这一跨学科领域的学生提供各种教育和支持活动，架起化学和生物学传统学科的桥梁。

This research program addresses the design of self-assembled stimulus responsive peptide complexes. Alpha helical coiled coils consist of two or more helical strands, wrapped into a superhelix, which bind to one another through interactions between core hydrophobic and surface hydrophilic amno acid sidechains. By introducing unnatural amino acids in coiled coil contexts, these studies will generate more diverse sequences, allowing the design of complexes suitable for next-generation peptide hydrogels. By engineering the appropriate behavior into isolated peptide complexes, this research addresses the design of "smart" materials that respond to physiological stimuli (pH, temperature, salt gradients). A formal program in Chemical Biology will be established, providing for the recruitment and training of students at both the undergraduate and graduate levels in the fundamentals and applications of work in this area, bridging the gap between chemistry and biology.With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program, Professor Alan Kennan, of the Department of Chemistry at Colorado State University, is carrying out fundamental studies related to the designed aggregation of proteins. By developing information about factors leading proteins to adopt particular structures, Professor Kennan designs assemblies of proteins that are expected to display unusual changes in response to their environment. These studies may lead to the development of "smart" materials that respond to physiological stimuli such as acidity, temperature and salt concentration. Professor Kennan will serve as the director of a new program in Chemical Biology, providing a variety of educational and support activities to recruit and train students in this interdisciplinary area, bridging the traditional disciplines of chemistry and biology.