Overview:
The goal of Raj lab is to develop new chemical reactions including catalysts for the synthesis of proteins, peptides and bioconjugates. Most importantly, we are interested in reactions and catalysts that work well in the aqueous medium. The Raj group also seeks chemical methods for synthesis of uniquely structured peptides, mimicking secondary structures, for inhibiting protein-protein interactions implicated in disease states. The unique structure of peptide is responsible for both the stability and biological activities. All of these efforts utilize organic chemistry tools, biochemical techniques and structural characterization.
Current Research Projects
New Reaction development for Chemical Ligation
Chemical ligation is very important reaction for synthesis of proteins, peptides and bioconjugates. It involves the formation of native amide “peptide” bond between two reactive ends. Current approaches for chemical ligation are limited by “slow rate” of ligation and requirement of specific residues at C-and N-terminus. We are interested in developing new chemical reactions for the synthesis of amide “peptide” bonds independent of terminal amino acid residues. Another goal of this project is to develop chemical methodologies for fast rate of ligation similar to enzymes.
Chemical Synthetic Approach to uniquely structured peptides for inhibiting protein-protein interactions
We are involved in the development of chemical strategies for the synthesis of uniquely structured peptides. The unique structure of these peptides provides them with extra-stability towards the degradation by enzymes in both vitro and in-vivo. The design of these peptides is inspired by some classes of antimicrobial peptides produced by microbes in nature as a defense mechanism against other species. It has been shown that unique structure of these peptides is responsible for both the stability and the biological activity. In addition, these peptides mimic particular secondary structures. We are interested in utilizing these uniquely structured peptides for inhibiting Protein-Protein Interactions (PPIs), which are implicated in diseases states and are mediated by secondary structures. We are also interested in developing chemical strategies to stabilize the secondary structure of peptides mainly focusing on β-hairpin and to utilize these β-sheet mimics to inhibit various PPI’s.
Catalytic approaches to biomolecules and chemical ligation
We are involved in developing new catalytic methods for synthesis of biological molecules. To achieve these goals, we focus on utilizing inexpensive and environmental friendly organocatalysts, which operate very well in the aqueous medium. We are also interested in developing catalytic approaches to ligation of proteins and peptides. Long-term goal of our research is to develop new reagents and catalysts for synthesis of peptides including difficult sequences on the solid support. These reagents or catalysts would increase the rate of traditional peptide synthesis.