Synthesis of Chemically-Modified Biological Molecules

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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.