Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors

Nicholas O Fischer, Catherine M. McIntosh, Joseph M. Simard, Vincent M. Rotello

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

Efficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as scaffolds for the binding and inhibition of chymotrypsin. In these studies anionically functionalized amphiphilic MMPCs were shown to inhibit chymotrypsin through a two-stage mechanism featuring fast reversible inhibition followed by a slower irreversible process. This interaction is very efficient, with a Ki app = 10.4 ± 1.3 nM. The MMPC-protein complex was characterized by CD, demonstrating an almost complete denaturation of the enzyme over time. Dynamic light scattering studies confirm that inhibition proceeds without substantial MMPC aggregation. The electrostatic nature of the engineered interactions provides a level of selectivity: little or no inhibition of function was observed with elastase, β-galactosidase, or cellular retinoic acid binding protein.

Original languageEnglish (US)
Pages (from-to)5018-5023
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number8
DOIs
StatePublished - Apr 16 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • General

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