Grant: Discovery Grants Program - Individual

Bacteria produce a range of carbohydrate-containing molecules with an impressive array of structural diversity. These glycoconjugates play critical roles in the life cycle of bacterial organisms, often modulating interactions with their environment. We will continue our work in the general area of bacterial glycans, and extend these investigations to new systems including plants. Three topics will be explored. 1. Synthetic Oligosaccharides as Tools for Studying Campylobacter jejuni Capsular Polysaccharide Biosynthesis. Campylobacter jejuni is an important food-borne pathogen and recent structural work has elucidated that bioactive polysaccharides produced by the organism have a variety of novel motifs. Among the most interesting are methyl phosphoramidate (MeOPN) moieties, which are rare in nature. We will synthesize fragments of the these polysaccharides for use in biosynthetic investigations focused on the origin of MeOPN groups. Also developed will be methodology for synthesizing what has been proposed to be the biosynthetic precursor, a CMP derivative. 2. Synthesis and Immunological Activity of Phenolic Glycolipids from Mycobacteria. Phenolic glycolipids (PGLs) are found in the cell wall of a number of mycobacterial strains including M. tuberculosis and M. leprae, the organism that causes leprosy. Sixteen unique PGLs have been isolated from pathogenic mycobacteria. Although known for many years, these molecules have attracted increased recent attention. We hypothesize that dissecting the biological roles of PGLs will be facilitated by access to a panel of synthetic PGLs analogues. We will prepare these compounds and then test their ability to modulate cytokine production. 3. Probing Oligofuranoside-Protein Interactions. The recognition of L-arabinofuranose-containing glycans by an L-arabinofuranoside will be characterized. We will use available X-ray data combined with chemical synthesis, binding studies and molecular biology to probe the recognition of carbohydrates containing five-membered rings by proteins. This is an area that has received very little attention.