Synthesis of Chemically-Modified Biological Molecules

DNA和RNA等分子是具有多种生物功能的糖-核酸聚合物。人们希望扩大核酸聚合物的结构，以改善其构效关系。最近，在国家科学研究委员会的资助下，我们合成了构建模块来生成核酸聚合物。在这笔拨款中，我们将合成各种新的糖核酸聚合物，这些聚合物可能具有有趣的生物学特性（项目a）。在本基金的第二个项目（项目B）中，我们将设计鞘氨醇和脑苷衍生物，它们是具有重要生物学作用的分子。例如，这些蜡质脂质分子在真核细胞的细胞膜中起着重要的结构作用。神经酰胺除了在细胞膜结构支持中的作用外，还被发现参与多种细胞信号通路。在这部分拨款中，将合成各种衍生物，以便更好地了解制备选择性SphK1和SphK2抑制剂的化学要求。最后，在拨款的最后一部分（C项目）中，我们将合成一些疏水分子（脑苷和鞘氨醇）并生成酰胺磷，以检测它们与基因沉默短干扰RNA结合后的效果。基于Synthose在糖和脂质化学方面的专业知识，以及安大略省理工大学（UOIT） Desaulniers博士研究小组在核酸化学方面的专业知识，新的化学修饰生物分子将被合成和研究。所描述的工作将在UOIT和Synthose之间的NSERC Engage资金之间建立桥梁，我们将产生独特的结构，可能具有有趣的未来商业价值。因此，通过开发新的化学修饰生物分子获得的新知识将为化学和生物技术领域提供令人兴奋的潜力。

Molecules such as DNA and RNA are sugar-nucleic acid polymers that have a variety of biological function. There is desire to expand the structure of nucleic acid polymers in order to improve the structure-activity relationship. Recently, funded via an NSERC Engage grant, we synthesized building blocks to generate nucleic acid polymers. In this grant, we will synthesize a variety of new sugar-nucleic acid polymers that may have interesting biological properties (Project A). In the second project of this grant (Project B), we will design sphingosine and cerebroside derivatives, which are molecules that have important biological roles. For example, these waxy lipid molecules play an important structural role within the cell membranes of eukaryotic cells. In addition to their role in structural cell membrane support ceramides have been found to participate in a variety of cell signalling pathways. In this portion of the grant, various derivatives will be synthesized in order to better understand the chemical requirements to make selective SphK1 and SphK2 inhibitors. Finally, in the last part of the grant (Project C), we will take some hydrophobic molecules synthesized (cerebroside and sphingosine) and generate phosphoramidites to examine their effect when conjugated to a gene-silencing short interfering RNA. Based on the expertise of Synthose in sugar and lipid chemistry, and the expertise in nucleic acid chemistry by Dr. Desaulniers' research group at the University of Ontario Institute of Technology (UOIT), new proposed chemically-modified biological molecules will be synthesized and studied. The work described will bridge the NSERC Engage funding between the UOIT and Synthose, and we will generate unique structures that may have interesting future commercial value. As such, the new knowledge gained through the development of new chemically-modified biological molecules will offer exciting potential for the chemistry and biotechnology fields.