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Faculty: Peter Andreana, Ph.D.

Research Synopsis:听Research interests in the Andreana group include natural product synthesis, carbohydrate-based diversity oriented synthesis (DOS), carbohydrate-based vaccines and combinatorial methods for high-throughput screening. The key underlying question for this research program is: How do carbohydrates modulate cellular function? In order to address this question, chemistry as the vector into biology is emphasized.

There are five major research directions our group currently pursues.

I. Synthesis of Naturally Occurring Carbohydrates / Polysaccharides
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 generate a clearer understanding of how these naturally synthesized molecules illicit immune responses via the MHCII pathway (See figure pathway听I).

II. Carbohydrate-Based, Diversity Oriented Synthesis
Another objective in our group seeks to examine a diversity oriented synthesis (DOS) approach toward the construction of a class of compounds containing carbohydrate scaffolds as potential therapeutic agents (See figure pathway听II).

III. Carbohydrate-Based Vaccines
Current carbohydrate-based vaccines, while effective, do not protect against the carrier protein and, therefore, an immunogenic response is heterogeneous in nature. Our objective is to prepare well-known carbohydrate antigens, such as the well-defined polysaccharide (Man9GlcNAc2-HIV gp120), in which the oligosaccharides are linked to a T-cell inducing ZPS for the development of carbohydrate-based vaccines (See figure pathway听III).

IV. Combinatorial Carbohydrate Libraries and Carbohydrate-Based Micro Arrays
To determine whether an alternating charge character is necessary to elicit a T-cell response, the Andreana group will take advantage of the solid support, split-pool concept of combinatorial chemistry and develop a carbohydrate-based library with electrostatic charge character. It is of great interest to determine, systematically, how the electrostatic charges of ZPSs interact with various modulators of APCs (See figure pathway听IV).

V. Small Molecule Synthesis (Green Chemistry)
The proposed small molecule synthesis ties in extremely well 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. 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 (See figure pathway听V).

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