Investigations into the Biological Activity of Two New NHC-Coinage Metal Complexes
Disciplines
Amino Acids, Peptides, and Proteins | Enzymes and Coenzymes | Inorganic Chemicals | Organic Chemicals
Abstract (300 words maximum)
Over the past few decades, N-heterocyclic carbenes (NHCs) have become a benchmark of organometallic chemistry. Due to their strong σ-donating and π-acceptor ability, NHC are not only great ligands in catalysis, but they are also exceptionally well suited to stabilize transition metal complexes in biological environments. Many NHC-transition metal complexes have been found to display biological activity such as anticancer, antimicrobial, antiseptic, antioxidants, and anti-inflammatory agents. This study targeted two NHC-coinage metal complexes which were screened for glutaredoxin (GRx) inhibition. Glutaredoxins (GRx) are part of a family of thioltransferases that uniquely reduce mixed disulfides with glutathione, using a critical cysteine thiolate residue in the active site. This thiolate is susceptible to alkylation causing inhibition of the enzyme. Preliminary studies show that the new coinage metal complexes are capable of irreversibly inhibiting GRx, demonstrated using a coupled assay system.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Daniela Tapu
Investigations into the Biological Activity of Two New NHC-Coinage Metal Complexes
Over the past few decades, N-heterocyclic carbenes (NHCs) have become a benchmark of organometallic chemistry. Due to their strong σ-donating and π-acceptor ability, NHC are not only great ligands in catalysis, but they are also exceptionally well suited to stabilize transition metal complexes in biological environments. Many NHC-transition metal complexes have been found to display biological activity such as anticancer, antimicrobial, antiseptic, antioxidants, and anti-inflammatory agents. This study targeted two NHC-coinage metal complexes which were screened for glutaredoxin (GRx) inhibition. Glutaredoxins (GRx) are part of a family of thioltransferases that uniquely reduce mixed disulfides with glutathione, using a critical cysteine thiolate residue in the active site. This thiolate is susceptible to alkylation causing inhibition of the enzyme. Preliminary studies show that the new coinage metal complexes are capable of irreversibly inhibiting GRx, demonstrated using a coupled assay system.