I-Corps: Selenium Nucleic Acids for Structure Determination, Drug Discovery and Commercialization

本项目计划开发和探索硒核酸在较长核酸及其蛋白质复合物的三维结构研究和药物发现，特别是药物靶点表征中的潜在价值。核酸及其蛋白质复合物已被认为是癌症治疗中的重要药物靶点。DNA是许多具有抗癌活性的小分子药物的常见靶点。DNA及其配体复合物的高分辨结构在药物设计、发现和机理研究中至关重要。X射线晶体学是测定这些大分子和配合物结构的最直接、最有力的工具之一。此外，晶体学是提供这些高分子结构信息的最佳策略之一。该研究小组正在开发新的硒策略，以提高核酸及其与配体（包括蛋白质和小分子）的复合物的结构分辨率，用于药物靶点研究和药物开发。该提案的总体目标是开发和商业化用于确定核酸及其与小分子药物的复合物的高分辨率晶体结构的SeNA策略（或潜在药物）和蛋白质复合物用于疾病研究（如癌症研究）和药物开发。硒核酸研究将提供对核酸化学和生物化学的见解，以及结构和功能特性，这对科学界和公众都有很大的兴趣。硒核酸可能导致新的材料和应用。此外，这一拟议项目将使人们能够广泛获得这些宝贵的新材料。这些潜在的发现可以鼓励它们的广泛使用，并允许更广泛地获得这些独特的材料进行功能和结构研究。

This project plans to develop and explore potential value of selenium nucleic acids in 3D structure studies and drug discovery of the longer nucleic acids and their protein complexes, especially drug target characterization. Nucleic acids and their protein complexes have been recognized as important drugs targets in cancer treatments. DNAs are frequent targets of many small-molecule drugs with anticancer activities. High-resolution structures of DNAs and their ligand complexes are critical in drug design, discovery, and mechanism study. X-ray crystallography is one of the most direct and powerful tools for structure determination of these macromolecules and complexes. Moreover, crystallography is one of the best strategies to provide structure information of these macromolecules with high resolutions. The research team is developing novel selenium strategies to increase structure resolutions of nucleic acids and their complexes with ligands (including proteins and small molecules) for drug target study and drug development. The overall goal of this proposal is to develop and commercialize the SeNA strategies for determining high-resolution crystal structures of nucleic acids and their complexes with small molecule drugs (or potential drugs) and protein complexes for disease study (such as cancer research) and drug development.Se-nucleic acid research will provide insights into nucleic acid chemistry and biochemistry, and the structural and functional properties, which are of great interest to scientific community as well as to the general public. Se-nucleic acids may lead to novel materials and applications. Furthermore, this proposed project will allow the widespread access to these valuable new materials. These potential discoveries could encourage their widespread use and allow broader access to these unique materials for function and structure studies.