Using Dynamic Combinatorial Chemistry to Find an Exclusive Molecular Receptor for Nitrotyrosine (2011)

Undergraduate: Adam Hill

Faculty Advisor: Marcey Waters
Department: Chemistry

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The goal of this research is to find a molecular receptor which will preferentially bind nitrotyrosine in the presence of tyrosine. Nitrotyrosine is an oxidative post translational modification which adds a nitro (-NO2) ortho to the phenol ring of tyrosine, and has been detected at increased levels in inflammatory, neurodegenerative and cardiovascular diseases. Current methods of detection for nitrotyrosine often give ambiguous results and are expensive and labor intensive. A molecular receptor which can exclusively bind nitrotyrosine in the presence of tyrosine (Tyr) would help to alleviate many of these issues. Dynamic combinatorial chemistry (DCC) will be used in this study to create a library of compounds in thermodynamic equilibrium from a set of monomers which can participate in reversible disulfide exchange. DCC allows for the guest molecule (a short model peptide containing either a tyrosine or nitrotyrosine residue) to amplify the receptor in the dynamic combinatorial library (DCL) to which it has the strongest binding. A set of 8 monomers based on aromatic rings of different sizes to allow for ?-? stacking interactions with nitrortyrosine have been synthesized and combined into DCLs. A handful of potential nitrotyrosine receptors have been identified and these compounds are currently being synthesized and purified on a semi-preparatory scale in order to quantitate their binding affinity to nitrotyrosine and tyrosine residues.