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Kevin Burgess; Research Projects

Our group is focused on two critical problems in contemporary biomedicinal chemistry.  Specifically, design of organic molecules to:

      1. perturb protein-protein interactions (PPIs); and,
      2. guide cytotoxic and imaging agents to tumor cells in vivo.

Perturbing PPIs.  There may be more thousands of viable protein-protein interaction (PPI) targets for medicinal chemistry, including many for tackling diseases for which there is currently no cure.  High throughput screening (HTS) is the most common approach to identify active small molecules, but it is expensive and, in the case of PPIs, the outcome is usually disappointing with respect to the number and quality of the hits that emerge.  In spite of this, HTS is used extensively for PPIs because they are so important.  Thus there is a substantial need for new techniques to obtain small molecules that perturb PPIs.  We have developed such a method, EKO (Exploring Key Orientations).

research graphic

Small Molecules To Target Cells.   Synthetic chemists have been preoccupied with making cytotoxic compounds but, in fact, there are many molecules that will kill cells.  In oncology, the main problem with most FDA approved drugs is that they have poor therapeutic indices, ie they kill healthy tissue almost as effectively as tumors.  In response there are many efforts to perturb biochemical pathways that are selectively upregulated in cancerous cells, ie target-oriented approaches to form compounds like kinase inhibitors.  Our hypothesis is that the next major phase in this area will be on small molecules to selectively target cells to deliver imaging or cytotoxic agents inside.   Most current research on cell-targeting involves antibodies; this strategy is useful but usually does not lead to intracellular delivery.  Conversely, small molecules can be used for intracellular delivery; the problem is how to design and validate substances that will do this.  Our group is developing methods and concepts to target both known and unknown cell surface receptors using chemotypes similar to the ones featured in the EKO approach outlined above.

Kevin Burgess is the Rachel Professor of Chemistry at Texas A&M University. His research interests focus on:

* design and applications of small molecules for disrupting protein-protein interactions

* applications of targeting and fluorescent probes in biotechnology

* rapid development of asymmetric organometallics catalysts and applications in syntheses of valuable chirons for organic syntheses

He is the author of a self-study book Organic Chemistry By Inquisition, and monthly contributor to Highlights in Chemistry and Industry.


PPI Project (pdf download)