TY - JOUR
T1 - Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors
AU - Fischer, Nicholas O
AU - McIntosh, Catherine M.
AU - Simard, Joseph M.
AU - Rotello, Vincent M.
PY - 2002/4/16
Y1 - 2002/4/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037117496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037117496&partnerID=8YFLogxK
U2 - 10.1073/pnas.082644099
DO - 10.1073/pnas.082644099
M3 - Article
C2 - 11929986
AN - SCOPUS:0037117496
VL - 99
SP - 5018
EP - 5023
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 8
ER -