The molecular mechanism of the ligand exchange reaction of an antibody against a glutathione-coated gold cluster

Abstract

The labeling of proteins with heavy atom clusters is of paramount importance in biomedical research, but its detailed molecular mechanism remains unknown. Here we uncover it for the particular case of the anti-influenza N9 neuraminidase NC10 antibody against a glutathione-coated gold cluster by means of ab initio QM/MM calculations. We show that the labeling reaction follows an associative double S2-like reaction mechanism, involving a proton transfer, with low activation barriers only if one of the two distinct peptide/peptidic ligands (the one that occupies the side position) is substituted. Positively charged residues in the vicinity of the incoming thiol result in strong interactions between the antibody and the AuMPC, favoring the ligand exchange reaction for suitable protein mutants. These results pave the way for future investigations aimed at engineering biomolecules to increase their reactivity towards a desired gold atom cluster.

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers

“…Together with geometrical shell closings (e.g., icosahedra, decahedra) and possible ligand‐protection, this causes that the physicochemical properties of AuNPs have a strong dependence on their size and shape . AuNPs are used in a broad spectrum of applications such as molecular recognition and specific binding to biomolecules with significant implications for biological and biomedical studies . The corresponding AuNPs are typically ligand‐protected where the surrounding side groups can be varied, and they are mainly responsible for the interaction with membranes.…”

Developing a Fluorescent Hybrid Nanobiosensor Based on Quantum Dots and Azoreductase Enzyme forMethyl Red Monitoring

“…The thiolic end displayed a strong electron affinity to the zinc in the outer ZnS shell, and thus the initial surface ligand could be replaced with MPA. Carboxyl group existing in the molecular structure also provided the water solubility to QDs because of its strong participation in hydrogen bond formation [51,52,[58][59][60] . The successful phase transfer of these nanoparticles after ligand exchange could be directly illustrated by the transparency of the resulting solutions.…”

Ligand exchange reactions on thiolate-protected gold nanoclusters

“…The initial reaction of this modification is a ligand exchange reactions of the anti-influenza N9 neuraminidase NC10 antibody against a glutathione ligand on a gold cluster as studied by means of ab initio QM / MM calculations. 87 Compared to the reaction with free thiol, the example displayed here concerns a large protein and may have two substitution modes as illustrated in Fig. 8 .…”