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Liberty Blue Customer Highlight: Dr. Champak Chatterjee

January 23, 2018

CEM recently had the opportunity to interview Dr. Champak Chatterjee, Associate Professor of Chemistry at the University of Washington, and Liberty Blue user.  Dr. Chatterjee obtained his Ph.D. in Chemistry from the University of Illinois at Urbana-Champaign and performed post-doctoral research at the Rockefeller University in New York City.  Dr. Chatterjee's independent research career has focused on Chemical Biology, with a special emphasis on chemical protein synthesis by native chemical ligation. His laboratory employs semisynthetic proteins as powerful molecular tools to elucidate the function and regulation of essential biochemical pathways in pathogenic bacteria and humans. Dr. Chatterjee joined the Department of Chemistry at the University of Washington in August 2010 because of its strength in Chemical Biology and its proximity to an excellent medical school with many strong departments including Biochemistry, Pharmacology and Medicinal Chemistry. "The depth and breadth of ongoing research at UW is truly awe-inspiring and I have benefited from many stimulating discussions and collaborations with faculty across campus."

 

Q: Could you provide a little background about your research and what attracted you to the specific area you are studying?

Dr. Chatterjee: My current research efforts are directed toward elucidating the mechanistic details underlying the regulation of eukaryotic gene transcription by post-translational modifications of histones and transcription factors. The approaches I have adopted to elucidate these mechanisms include peptide and protein synthesis, well-defined biochemical assays with purified human enzymes, and cell-based experiments including high-throughput RNA and DNA sequencing.  What attracted me to this area of research is the amazing diversity of reversible organic chemistry that is undertaken on histones and transcription factors by a large family of chromatin-associated enzymes. I was hooked by the subtlety of chemical changes in these proteins that lead to dramatic effects on cellular fates. My lab is applying protein chemistry toward unraveling the post-translational modification (PTM) “code” of these two key protein classes.

 

Q: What goals do you hope to accomplish and what problems do you want to solve with your research?

Dr. Chatterjee: The immediate goals that I hope to accomplish are to understand how modification of histones and the transcription factor p53 by the small ubiquitin-like modifier (SUMO) protein lead to changes in their function and ultimately to changes in gene transcription. Understanding the mechanism of gene regulation by reversible PTMs will provide avenues for therapeutic intervention in cancers arising from the misregulation of these PTMs. The problem in tackling these questions lies in the challenge of accessing uniformly modified proteins in sufficient quantities for detailed biochemical and biophysical studies. We are addressing this problem by developing new chemical strategies to produce homogenously modified proteins in milligram quantities.

                 

Q: How does solid-phase peptide synthesis (SPPS) fit into your research goals? What impact does improving SPPS have for your research?

Dr. Chatterjee: Solid-phase peptide synthesis (SPPS) is a synthetic technique integral to our goals. We generate site-specifically modified proteins by joining various chemically modified peptide fragments, synthesized by SPPS, using native chemical ligation. Therefore, developing facile methods for SPPS and reducing the number of post-synthetic steps greatly increases the yield of our final modified proteins. The MEGA approach, pioneered by Patrick Shelton in my lab, is a particularly appealing strategy for SPPS that requires minimal peptide manipulation after assembly.

 

Q: How has the Liberty Blue peptide synthesizer and its HE-SPPS methods been useful for your research to date?

Dr. Chatterjee: The Liberty Blue synthesizer is a powerful instrument that greatly reduces the time required for peptide synthesis and permits optimization of various steps during peptide assembly. The Liberty’s rapid coupling and deprotection cycles and compatibility with a wide-range of resins and linkers, including the MEGA resin, enable the synthesis of long peptides (30-60 amino acids in my own labs) in a few hours. The ability to finely tweak every step of the synthesis, from the duration and temperature of coupling/deprotection to the specific combinations of reagents, makes optimizing a synthesis easy and ensures high yields of the final crude peptide. We have benefited from using the Liberty Blue with our MEGA resin to make a 35-mer peptide thioester and also used it to synthesize a bioactive analog of the Sunflower Trypsin Inhibitor peptide. My students truly appreciate the modularity and easy programmability of the Liberty Blue, which has significantly facilitated their training in the art of peptide synthesis.

 

Patrick Shelton
 Patrick Shelton, Chatterjee Research Team

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