Development of a novel technology for in vitro evaluation of RNA/DNA-targeted compounds

开发 RNA/DNA 靶向化合物体外评价新技术

• 批准号: 514863-2017
• 负责人: Zenkina, Olena
• 金额: $ 1.82万
• 依托单位: University of Ontario Institute of Technology
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=640166
• 关键词: Development; novel; technology; vitro; evaluation

The high adaptation ability of bacteria to existing antibacterial agents is a major issue that requires newapproaches in the design of novel antibiotics. One such approach, used by a small hi-tech Canadian companyOtava Ltd, is based on selective binding of chemical molecules to specific bacterial RNA or DNA sequences.This binding leads to depletion of bacteria growth and reproduction. Here we propose a new methodology forchemical screening and evaluation of compounds designed to selectively bind microbial RNA/DNA. Usingcomputer simulation methods, Otava Inc. has created novel libraries of fine organic compounds that matchphysical and structural parameters of typical RNA/DNA targets. Further screening steps aimed to determinethe most promising pre-antibiotics are very expensive, time-consuming, and require special biohazardaccredited laboratory facilities. For now, Otava Inc. needs to collaborate with large pharmaceutical companiesto perform in vivo screening of the activity of each compound they produce. This approach significantlyincreases the turnover time between the development of the product and commercialization of the findings. Thelack of the fast screening method to evaluate the activity of their compounds is hampering their researchabilities and limiting their ability to grow. We believe that we will be able to develop a purely chemical methodto estimate the potential of organic compounds from the library to act as selective inhibitors of duplication ofspecific bacterial DNA sequences. This will allow eliminating less effective compounds and proposing highquality competitive commercial products to the pharmaceutical industry. We expect this to allow the smallOntario company to grow and compete with larger international companies. It is not a secret that it is verydifficult for Canadian companies to compete with third-world countries that over-use cheap labor power andmaintain poor working environments to reduce the cost of their products. We want to use our scientificstrengths to optimize the process of pharmaceutical screening and allow Canadian companies to intensify theirresearch power while maintaining high standards of work environment and living.

细菌对现有抗菌剂的高度适应能力是一个主要问题，需要新的方法来设计新的抗生素。加拿大一家小型高科技公司Otava Ltd使用的一种方法是，将化学分子选择性地与特定的细菌RNA或DNA序列结合，这种结合导致细菌生长和繁殖的枯竭。在这里，我们提出了一种新的方法化学筛选和评价的化合物，旨在选择性地结合微生物RNA/DNA。利用计算机模拟方法，Otava Inc.已经创建了精细有机化合物的新库，这些化合物与典型RNA/DNA靶标的物理和结构参数相匹配。进一步的筛选步骤旨在确定最有希望的前抗生素是非常昂贵的，耗时的，并需要特殊的生物危害认证的实验室设施。目前，Otava Inc.需要与大型制药公司合作，对他们生产的每种化合物的活性进行体内筛选。这种方法大大增加了产品开发和研究结果商业化之间的周转时间。缺乏快速筛选方法来评估其化合物的活性，阻碍了其研究能力并限制了其发展能力。我们相信，我们将能够开发出一种纯化学方法来估计来自文库的有机化合物作为特定细菌DNA序列复制的选择性抑制剂的潜力。这将允许消除不太有效的化合物，并向制药行业提出高质量的竞争性商业产品。我们希望这能让安大略省的小公司成长并与更大的国际公司竞争。这不是一个秘密，这是非常困难的加拿大公司与第三世界国家竞争过度使用廉价劳动力和维护恶劣的工作环境，以降低其产品的成本.我们希望利用我们的科学优势来优化药物筛选过程，让加拿大公司在保持高标准的工作环境和生活的同时，加强他们的研究能力。