The Verani group has demonstrated that metal complexes inhibit chemotrypsin-like (CT) activity associated with the 26S proteasome in purified samples, cell extracts, intact cells, and in-vivo.This CT-inhibition has been studied with several [MII/III(L)2]0/+ complexes where the ligand is an asymmetric and deprotonated iodo-substituted [NpyNamOphen] chelate. Except for [NiII(L)2], other complexes with Ga(III), Cu(II), Zn(II), and Co(II/III) show good activity that seems associated with the nature of the ligand substituents, complex topology, metal inertness, and its redox properties. Some species also show selectivity towards cancer cells.A direct proteasome/complex interaction was proposed, similar to that reported for known proteasome inhibitors. This interaction requires partial or total ligand dissociation. In this presentation we discuss new complexes with redox active and redox-inactive cations, as well as a deeper look into the role of bioreductive activation.  Due to an increased proteasomal activity in tumor cells, this observation has considerable therapeutic relevance. Support: Karmanos, WSU, NSF

Evaluation of interactions between the proteasome and metal complexes

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.