The Andreana Research Group

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Research Synopsis: Research interests in the Andreana Research Group include natural and natural-product-like synthesis, carbohydrate-based vaccine design and development and small molecule combinatorial methods for high-throughput screening. The key underlying question for our research program is: How do carbohydrates and small molecules modulate cellular function? In order to address this question, chemistry as the vector into biology is emphasized.

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One objective is to prepare well-defined zwitterionic polysaccharides (ZPS), in which the oligosaccharide is amenable to chemical modifications for the development of bioprobes. The long  term goal is to elucidate a better under-standing of how these synthesized molecules illicit immune responses presumably via the MHCII pathway.

Another objective in our group is to examine a diversity oriented synthesis (DOS) approach toward the construction of a class of compounds containing carbohydrate scaffolds as potential therapeutic agents.  DOS is enabling because it provides a platform for fast and facile modifications of carbon skeleton frameworks.

To understand molecular structure and function pertaining to biological systems, the Andreana group will take advantage of solid support, split-pool concept of combinatorial chemistry and develop carbohydrate-based libraries. For example, it is of great interest to determine, systematically, how the electrostatic charges of ZPSs interact with various modulators of immune cells.

Our small molecule synthesis program ties in with a platform for the development of modulators (Chemical Genetics) of the immune pathway to determine mechanistic insights of carbohydrate processing in the antigen presenting cell or dendrite cell. For example, the tyrosine kinase p56 (lck) is present in T-cells and is known to be required to initiate the activation response from the T-cell receptor (TCR) intracellular domain to other signaling proteins. T-cells that lack lck are unable to respond to stimulation through the TCR.

In the past several decades, there has been an emergence of increasingly drug-resistant strains of TB bacteria. Multi-drug-resistance (MDR) TB is a major concern as at least 2 of the best anti-TB drugs: isoniazid and rifampin are rendered ineffective. In under-standing biosynthetic pathways and en-zymatic mechanisms, synthetic sub-strates in conjunction with rationally designed inhibitors will be used to target essential enzymes known for the survival of TB.