Welcome to Chow Lab Research Exploring the RNA World, One Modification at a Time
"All for One and One for All "
Our Approach
Project 1 - Generate ligands that target the PDZ domain family of proteins and to characterize the thermodynamics of binding. In this endeavor very challenging carboxy-terminal peptide display on solid support have been developed and these strategies have been modified to be used in combinational libraries. These compounds have been used in cellular studies and have served as molecular probes to decipher biological functions of PDZ-mediated binding events.
Project 2 - Novel assay development for solution phase and solid phase screening of large chemical libraries from combinatorial synthetic schemes or compound libraries. On-bead assay schemes have been developed for high-throughput screening of large libraries.
Project 3- Finding antimicrobial drug leads and new classes of antimicrobial therapeutics that target the ribosome. This project involves a combination of strategically designed organic compounds, cyclic peptides and on-bead combinatorial libraries which have been synthesized and screened to evaluate binding to selected regions of the ribosome as well as other functionally important RNA biomolecules.
All of my projects involve the synthesis of peptide derivatives and their applications in interesting biological systems. The central focus of my project has been is to characterize the thermodynamics of binding to PDZ proteins (co-advisor: Dr. Mark Spaller). These compounds can be used in cellular studies and serve as molecular probes to decipher biological functions of PDZ-mediated binding events. On the way to finding novel ligands that target PDZ domains, novel assays have been developed in solution phase and solid phase to screen large chemical libraries from combinatorial synthetic schemes or compound libraries. On-bead assay schemes have been developed for high-throughput screening of large libraries. Another project, aims at finding antimicrobial drug leads and new classes of antimicrobial therapeutics that target the ribosome. This project involves a combination of strategically designed organic compounds, cyclic peptides and on-bead combinatorial libraries that have been synthesized and screened to evaluate binding to selected regions of the ribosome. Supported by NIH GM054632.
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Figure 1: A) Schematic representation of a cleavable on-bead library member B) Detailed view of H69 (purple) interactions with the A site decording region (green) and minor groove of A site bound tRNA and the D stem of P site bound tRNA (PDB ID:2I1C and 1VS9).
