Event
Organic Chemistry Seminar; Dr. Monika Raj, Auburn University
Inquiries please contact Rosa M. Vargas rvargas@sas.upenn.edu
Chemical Tools for Selective Recognition of Posttranslational Modifications and Enzymes
-Selective modification of biomolecules provides scientists with an effective tool for a multitude of bioanalytical, therapeutic, biological and bioengineering applications. However, chemical strategies that can target a particular functional group at a single site in the presence of reactive amino acid side chains on protein surfaces are limited. In this seminar, I will introduce the research in the Raj Lab at AU. First, I will focus on our efforts to develop novel multicomponent bioconjugation approach for selective labeling of proteins containing secondary amines. This method does not require any genetic engineering of the protein target and protection of the side chains of other amino acids. The resulting bioconjugation reaction leads to the formation of a highly stable C-C bond at the site of the conjugation. This method is employed for labeling monomethyl lysine containing posttranslational modifications (PTMs) on proteins with various cargoes. The dysregulation of monomethyl lysine PTMs has been linked to a variety of different biological malfunctions, yet the chemical methods for selective detection of mono methyl lysine PTMs are still lacking. I will explain how our method can be used for detecting monomethyl lysine PTMs thus has the potential to further our understanding of the role of monomethylated lysine containing PTMs in regulating various cellular signaling processes.
Second, I will talk about the design and synthesis of molecular imaging agents for determining the role and subcellular distribution of lysine eraser enzymes such as lysine demethylases. We anticipate that these molecular imaging agents could lead to the discovery of novel protein biomarkers and new therapies for the treatment of diseases mediated by lysine demethylases.