Examining the Conformational Preferences of Pentofuranosides

Bacteria that cause diseases such as tuberculosis and leprosy use unique carbohydrates as part of their natural defenses. Since these carbohydrates are not used in mammalian cells, they are natural targets for new antibiotics. The very flexible shapes of these carbohydrates are not well understood. A better understanding of the flexible shape, or conformational preference, of these carbohydrates will strengthen our ability to design these new antibiotics. This is especially important because many of these bacteria are developing multiple-drug-resistant strains.

Research in the Rhoad group falls into two categories: computational and synthetic/spectroscopic. Our computational methods build models that are designed to predict the conformational preference of the simple protected sugars. The synthetic/spectroscopic derivatizes simple sugars and then does close measurements of the parameters influenced by the conformation—specifically proton-proton coupling constants in nuclear magnetic resonance spectroscopy. The measured versus calculated parameters are compared to determine the success of the computational modelling.