Foldamers with Heterogeneous Backbones

具有异构骨架的折叠器

• 批准号: 0140621
• 负责人: Samuel Gellman
• 金额: $ 49万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0140621&HistoricalAwards=false
• 关键词: Foldamers; Heterogeneous; Backbones

The objective of this work is to prepare foldamers (unnatural oligomers or biopolymers) that adopt defined and predictable conformations. They will synthesize and conformationally analyze a number of heterogeneous oligomers where one type of monomer (such as alpha amino acids) provides functional diversity while another type of monomer (cyclically constrained beta or gamma amino acids) provides conformational specificity and stability. Homogeneous oligomers containing just gamma amino acids will also be synthesized and analyzed as will oligomers that are heterogeneous due to monomer stereochemistry variations. Once new oligomers are identified that adopt specific conformations in aqueous solutions, they will be tested for stability to proteolytic degradation and for their ability to move across membranes of living cells. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Samuel H. Gellman of the Department of Chemistry at the University of Wisconsin. Dr. Gellman will explore the synthesis of new proteins using combinations of natural and unnatural amino acids. These proteins will then be screened to look for those which adopt specific conformations (shapes) in aqueous (water based) solutions. Those which do fold into specific and predictable shapes will be screened for their affinity to biomolecular targets. In particular, they will be screened for their ability to disrupt other protein-protein interactions. Controlled disruption of protein-protein interactions has possible future biomedical science applications in cancer prevention. Students trained as a result of working on this project will gain experience in bioorganic and supramolecular organic chemistry, hence they will have skills needed by the pharmaceutical and speciality chemicals industries.

这项工作的目标是制备采用确定和可预测构象的折叠体(非天然低聚物或生物聚合物)。他们将合成和构象分析许多非均相低聚物，其中一种类型的单体(如α氨基酸)提供功能多样性，而另一种类型的单体(循环约束的β或伽马氨基酸)提供构象特异性和稳定性。还将合成和分析仅含有伽马氨基酸的均相低聚物，以及由于单体立体化学变化而异相的低聚物。一旦确定了在水溶液中采用特定构象的新低聚物，将测试它们对蛋白质降解的稳定性以及它们穿越活细胞膜的能力。通过这一奖项，有机和高分子化学项目支持了威斯康星大学化学系的塞缪尔·H·盖尔曼博士的研究。盖尔曼博士将探索使用天然和非天然氨基酸的组合来合成新的蛋白质。然后对这些蛋白质进行筛选，以寻找那些在水(水基)溶液中采用特定构象(形状)的蛋白质。那些确实折叠成特定和可预测的形状的细胞将被筛选，以确定它们与生物分子靶标的亲和力。特别是，将对它们破坏其他蛋白质-蛋白质相互作用的能力进行筛查。蛋白质-蛋白质相互作用的受控破坏有可能在未来的生物医学科学中应用于癌症预防。通过这个项目培训的学生将获得生物有机化学和超分子有机化学方面的经验，因此他们将拥有制药和特种化学品行业所需的技能。