Developing Dirhodium-Complexes for Protein Inhibition and Modification & Copper-Catalyzed Remote Chlorination of Alkyl-Hydroperoxides

• Main Author: Kundu, Rituparna
• Other Authors: Ball, Zachary T.
• Format: Others
• Language: English
• Published: 2013
• Subjects: metallopeptides; protein–protein interactions; inhibitors; cysteine modification; rhodium; sp3 remote C-H activation
• Online Access: http://hdl.handle.net/1911/71980

The work describes the development of a new class of protein-inhibitors for protein-protein interactions, based on metallopeptides comprised of a dirhodium metal center. The metal incorporation in the peptide sequence leads to high increase in binding affinity of the inhibitors. The source of this strong affinity is the interaction of histidine on the protein surface with the rhodium center. In addition to this work, rhodium-based small molecule inhibitors for FK-506 binding proteins are investigated. Also, methodology for rhodium-catalyzed modification of proteins containing surface cysteine has been developed where a simple rhodium(II) complex catalyzes cysteine modification with diazo reagents. The reaction is marked by clean cysteine selectivity and mild reaction conditions. The resulting linkage is significantly more stable in human plasma serum, when compared to common maleimide reagents. Apart from this body of work in chemical-biology, the thesis contains the discussion of development of copper-catalyzed remote chlorination of alkyl hydroperoxides. The atom transfer chlorination utilizes simple ammonium chloride salts as the chlorine source and the internal redox process requires no external redox reagents.