title: Tunable reactivation of nanoparticle-inhibited beta-galactosidase by glutathione at intracellular concentrations.
abstract: Positively charged trimethylammonium-functionalized mixed monolayer protected clusters (MMPCs) of different chain lengths (C(8) and C(11)) have been used to bind beta-galactosidase through complementary electrostatic interactions, resulting in complete enzyme inhibition. This inhibition can be reversed in vitro by intracellular concentrations of glutathione (GSH), the main thiol component of the cell. The restoration of activity depends on the chain length of the monolayer. The activity of enzyme bound to particles with C(8) monolayer was completely restored by intracellular concentrations (1-10 mM) of GSH; however, little or no release was observed at extracellular GSH concentrations. In contrast, no restoration was observed for enzyme bound to the C(11) particles at any of the concentrations studied. Taken together, these studies demonstrate that the GSH-mediated release of enzymes bound to MMPCs can be tuned through the structure of the monolayer, a significant tool for protein and drug delivery applications.
authors.affiliation: Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, USA.
authors.forename: Ayush
authors.initials: A
authors.lastname: Verma
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Simard
authors.forename: Joseph W E
authors.initials: JW
authors.lastname: Worrall
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Rotello
mesh_terms: D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D049329:Nanostructures; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D000644:Quaternary Ammonium Compounds; D001616:beta-Galactosidase; D005978:Glutathione