ORGN 577 |
Mediation of protein activity using nanoparticle-based receptors
| Nicholas O. Fischer1, Catherine McIntosh Goodman1, Ayush Verma1, Joseph M. Simard1, D. Joseph Jerry2, and Vincent M Rotello1. (1) Department of Chemistry, University of Massachusetts, 710 N. Pleasant St., Amherst, MA 01003, (2) Department of Vet. and Animal Science, University of Massachusetts, Amherst |
Control of protein activity using synthetic receptors provides an important tool for mediating cellular activities. Protein surface binding allows targeting of a large range of proteins inaccessible to small molecule inhibitors, including those capable of protein-protein interactions and homodimerization. Using nanometer-scale mixed monolayer protected gold clusters (MMPCs) as macromolecular scaffolds, we have shown surface binding and inhibition of a model enzyme, chymotrypsin (ChT). Initial studies involved surface binding of ChT using anionic functionalized MMPCs. At ChT:MMPC ratios of 4:1, complete enzymatic inhibition was accomplished by a two-step mechanism: initial binding followed by a slow conformational change. By modifying the nanoparticle monolayer with cationic surfactants in situ, 65% of original enzymatic activity was restored. To investigate the use of MMPCs in more complex systems, the efficacy of nanoparticle-mediated disruption of protein-protein interactions is being tested on the HDM2-p53 model system, and will be discussed. |
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Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses
11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster
Sci-Mix
8:00 PM-10:00 PM, Monday, September 8, 2003 Javits Convention Center -- North Pavillion, Sci-Mix
Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003
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