Interactions of Trehalose wth Model Folate Compounds

Folate (vitamin B9) is an essential element in cellular metabolism. Folate is obtained from dietary intake, as the human body is unable to produce it, and it is required for the synthesis of many basic subunits used to compose both DNA and RNA. Previous studies have shown that folate interacts weakly with osmolytes, small molecular weight compounds produced by the cell when under stress, when the cell is crowded with them. Moreover, it has also been demonstrated that there is weaker binding between dihydrofolate reductase and dihydrofolate in the presence of these osmolytes and when the cell is under osmotic stress. This is an interesting finding when it comes to developing better anti-folate drug therapies that help eliminate unwanted cells from the body (i.e. bacterial and cancer). Because of these results, we are now interested in the mechanisms through which these enzyme-osmolyte interactions occur. This study uses vapor pressure osmometry to determine the type of interactions that occur between trehalose (a common cellular osmolyte) and various compounds that mimic functional groups found on folate. Through our studies, we have found positive preferential interaction coefficients for reactions between trehalose and various amino acids, amino acid salts, amides, carboxylic acids, and carboxylate salts, meaning that these compounds prefer to interact with water rather than trehalose. Using these results we will be able to understand how trehalose interacts with various atom types and how these atoms can contribute to cellular interactions and processes.