With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Marcey Waters from the University of North Carolina at Chapel Hill to study the fundamental molecular recognition properties of a set of synthetic receptors for each of the methylation states of lysine (Lys) and arginine (Arg), which are protein modifications involved in the control of gene expression. The receptors will be developed using Dynamic Combinatorial Chemistry, which will allow for rapid identification of a set of differentially selective hosts. Comprehensive mechanistic studies will be performed in which both the host and guest are varied that will provide insight into mechanisms for selective recognition between closely related guests in aqueous solution. Lastly, these same receptors will be used in indicator displacement assays coupled with pattern recognition to characterize the enzymes that methylate Lys, providing new insight into these biological pathways.
Molecular recognition, which involves the interaction of two (bio)molecules through a set of weak intermolecular forces called non-covalent interactions, is critical to virtually all biological function, including the interactions of proteins with other proteins, biomolecules, and inhibitors. However, the ability to predict the set of non-covalent interactions that will give rise to a particular molecular recognition event with a certain binding affinity and selectivity is still not possible. This work will provide a systematic study of a set of biologically relevant molecular recognition events to gain mechanistic insight into the features that provide both affinity and selectivity. This research will educate both graduate students and undergraduate students in organic, analytical, supramolecular chemistry, and biochemistry, providing a strong interdisciplinary background, which is necessary in an increasingly interdisciplinary workforce. This work will also introduce underrepresented high school and college students to interdisciplinary research.
