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，以改善结构-活性关系。最近，在NSERC Engage赠款的资助下，我们合成了构建块来生成核酸聚合物。在这笔赠款中，我们将合成各种可能具有有趣生物特性的新型糖-核酸聚合物(项目A)。在这笔赠款的第二个项目(B项目)中，我们将设计鞘氨醇和脑苷脂的衍生物，这是具有重要生物学作用的分子。例如，这些蜡质脂分子在真核细胞的细胞膜中起着重要的结构作用。神经酰胺除了在结构细胞膜支持中的作用外，还被发现参与了多种细胞信号通路。在赠款的这一部分，将合成各种衍生物，以更好地了解制造选择性SphK1和SphK2抑制剂的化学要求。最后，在资助的最后部分(项目C)，我们将合成一些疏水分子(脑苷脂和鞘氨醇)，并生成亚磷酰胺，以检测它们与基因沉默的短干扰RNA的作用。基于Syntheres在糖和脂肪化学方面的专业知识，以及安大略大学理工学院(UOIT)Desaulniers博士的研究小组在核酸化学方面的专业知识，将合成和研究新提出的化学修饰生物分子。所描述的工作将在UOIT和Synther之间架起NSERC Engage资金的桥梁，我们将产生可能具有有趣的未来商业价值的独特结构。因此，通过开发新的化学修饰生物分子而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.