This Core will provide synthetic chemistry in the following areas: 1. Trehalose and cord factor analogs designed to inhibit the mycolyltransferase activity of the antigen 85 complex which will provide models for tuberculosis drugs and also information relevant to the final pathways for mycolic acid deposition (Project 1;
Specific Aim 3). 2. Competitive inhibitors of key enzymes responsible for the synthesis of mycolic acid such as some of the desaturases (Project 1). 3. Transition state analogs designed to inhibit rhamnopyranosyl, arabinofuranosyl, and galactofuranosyl transferases, facilitating assay development (Project 4). 4. Synthesis of radiolabeled arabinofuranosyl nucleotides in order to see whether they are the direct and only precursors of the Araf unit in decaprenyl-P-Araf (C50-P-Araf), itself the source of polymerized Araf, facilitating assay development (Project 4). 5. Synthesis of [1-14C]-beta- D-arabinofuranosyl-1-mono-phosporyl decaprenyl (C50-P-[14C] Araf) to study arabinosyltransferases as targets for drug development (Project 4). 6. Synthesis of simple glycosyl group acceptors, to study aspects of cell wall biosynthesis, specifically biogenesis of the arabinan and galactan segments and inhibition of these steps (Project 4).
