Tunable inhibition and denaturation of alpha-chymotrypsin with amino acid-functionalized gold nanoparticles.
Water-soluble gold nanoparticles bearing diverse l-amino acid terminals have been fabricated to probe the effect of receptor surface on protein surface binding. The interaction of these nanoparticles with alpha-chymotrypsin (ChT) was investigated by activity assay, gel electrophoresis, zeta-potential, circular dichroism, and fluorescence spectroscopy. The results show that both electrostatic and hydrophobic interactions between the hydrophobic patches of receptors and the protein contribute to the stability of the complex. The microscopic binding constants for these receptor-protein systems are 10(6)-10(7) M(-1), with the capacity of the nanoparticle receptors to bind proteins determined by both their surface area and their surface charge density. Furthermore, it is found that the hydrophilic side chains destabilize the ChT structure through either competitive hydrogen bonding or breakage of salt bridges, whereas denaturation was much slower with hydrophobic amino acid side chains. Significantly, correlation between the hydrophobicity index of amino acid side chains and the binding affinity and denaturation rates was observed.
You
Chang-Cheng
CC
Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, Massachusetts 01003, USA.
De
Mrinmoy
M
Han
Gang
G
Rotello
Vincent M
VM
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002942:Circular Dichroism; D006046:Gold / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011489:Protein Denaturation / Q000187:drug effects; D013499:Surface Properties; D013997:Time Factors
D000596:Amino Acids; D008024:Ligands; D006046:Gold; D002918:Chymotrypsin; C117608:alpha-chymotrypsin