Self-Assemble and Programmable Nucleus Permeable Polyamides that Target Specific DNA Sequences with Slow Off-rates and High Affinity: Development of a Molecular Tool Kit

在化学学部有机动力学项目的支持下，密歇根州荷兰霍普学院的Moses Lee教授和乔治亚州立大学的W. David Wilson教授将开发出一类具有极好的结合亲和力和序列特异性的H-pin聚酰胺，并开发出一种新的策略来提高细胞通透性。在细胞核DNA结合促进？策略。这个项目的成功成果将对小分子- dna相互作用和控制基因表达的能力产生深远的影响。作为潜在的药物和DNA靶向诊断试剂，它最终将促进个性化医疗领域的进步。最近的工作导致了新化合物的设计，如聚酰胺类似物的distamycin，它能够识别基因启动子中的特定DNA序列。这些化合物通常难以进入细胞并在细胞核中定位。这种生物障碍一直是推进聚酰胺领域的主要绊脚石，化学和生物界正在努力克服这一物理障碍。这项工作将开发新的策略和探索基础科学，使科学家能够识别细胞中的特定基因并控制其功能。这项由霍普学院的李教授和乔治亚州立大学的w·大卫·威尔逊教授提出的建议具有更广泛的影响。它通过研究主题培养跨学科的学习，学生将学习化学，生物化学，分子和细胞生物学的各个分支学科。这将更好地为未来教育学生，并有助于确保美国的安全。竞争优势。此外，将特别强调培训妇女和来自科学领域代表性不足群体的学生。李教授和威尔逊教授在吸引这些学生参与他们的研究项目方面有着长期而成功的记录。学生将从两年制社区学院或霍普学院招收。通过参与美国国家科学基金会资助的s - stem项目或芝加哥社区学院联盟的美国国家科学基金会本科研究合作项目（URC）。高中生也将有机会通过希望学院的跨文化研究项目（REACH）参与到这个项目中来。

With the support of the Organic Dynamics Program in the Chemistry Division, Professor Moses Lee at Hope College in Holland, Michigan and Professor W. David Wilson at Georgia State University will develop a class of H-pin polyamides that possess superb binding affinities and sequence specificity, and develop a new strategy for improving cell permeability using a new ?in nucleus DNA binding promoted? strategy. A successful outcome from this project will have a profound impact in the area of small-molecule-DNA interactions and the ability to control the gene expression. It will ultimately contribute to the advancement of the personalized medicine field, as potential medicines and DNA targeted diagnostic agents. Recent work has led to the design of novel compounds, such as the polyamide analogs of distamycin, which are capable of recognizing specific DNA sequences in the promoters of genes. These compounds generally have difficulty in entering cells and localizing in the nucleus. This biological barrier has been the major stumbling block in advancing the polyamide field and there is a major effort among the chemistry and biology communities to overcome this physical obstacle. This work will develop new strategies and explore fundamental science that will enable scientists to recognize specific genes in cells and control their function.This proposal by Professor Lee at Hope College and Professor W. David Wilson at Georgia State University has a strong broader impacts component. It fosters an interdisciplinary learning through research theme in which students will learn various sub-disciplines of chemistry, biochemistry, molecular and cell biology. This will better educate students for the future and help to ensure America?s competitive edge. In addition, special emphasis will be placed on the training of woman and students from groups underrepresented in the sciences. Professors Lee and Wilson have a long and successful record of engaging these students in their research programs. Students will be recruited from two-year community colleges either through Hope College?s NSF funded S-STEM program or through participation in the NSF Undergraduate Research Collaboratives (URC) program of the Chicago Community Colleges Consortium. High school students will also have an opportunity to participate in this project through the Hope College program called Research Across Cultures at Hope (REACH).