Peptide‐Gold Nanoparticle Conjugates as Sequential Cascade Catalysts

Abstract

Combining bio-and chemocatalysis in one pot is a challenging task due to the necessity to ensure compatible reaction conditions, as well as reagent tolerance, for the catalytic components. Here we present a peptide-gold nanoparticle conjugate that combines esterase (biocatalysis) and hydrogenation (chemocatalysis) activities under the same set of aqueous reaction conditions. The self-assembled peptide-mono-layer acts as an esterase mimic and shows positive cooperativity in substrate binding, an important feature used by nature to regulate catalytic activities of enzymes. The gold nanoparticle surface catalyzes the reduction of a nitro-containing substrate to an amine product. This study opens up a new avenue in the design of peptide-metal nanoparticle catalysts with enzyme-like properties for efficient one-pot reactions.

Peptide–Gold Nanoparticle Conjugates as Artificial Carbonic Anhydrase Mimics

“…By applying supernatant analysis, the mean peptide loading per nanoparticle was determined to be 859 peptides/Au-NP. This corresponds to an average peptide density of 2.26 pep/nm 2 , which is consistent with literature reported peptide densities in the range of 1.41-2.55 pep/nm 2 , depending on the peptide length [9,11,22,23]. As the formation of β-sheets is a prerequisite for the generation of the 3-His Zn(II)-binding site, and thus the successful coordination of Zn(II) [19], circular dichroism (CD) spectroscopy was performed in order to assess the secondary structure of (un)conjugated IHQ-NP and its Zn(II)dependency.…”

“…While the dependence of unconjugated Zn(II)-/IHQ-NP-catalyzed 4-NPA hydrolysis on 4-NPA concentration displays hyperbolic behavior (Figure 3a), which is in accordance with the Michaelis-Menten theory, sigmoidal behavior was observed for Zn(II)-/Au@IHQ-NP ( Figure 3b). A sigmoidal profile indicates a positive cooperative effect for the binding of substrate molecules among individual active sites and has been previously observed to be an effect evoked by the conjugation and the resulting high peptide density within the peptide monolayer [9,11]. Positive cooperativity in substrate binding is classified as a regulatory mechanism also found in nature.…”

“…Among several approaches used to create nanozymes [4,5], the self-assembly of thiolated ligands onto the surface of gold nanoparticles (Au-NPs) to obtain monolayer-protected gold clusters (Au-MPCs) has emerged as a powerful strategy [6]. In particular, the conjugation of peptides on to the surface of gold nanoparticles to yield peptide-gold nanoparticle conjugates (Pep-Au-NPs) expanded the possibilities for the design of artificial enzymes [7][8][9][10]. Peptides are available at low cost by solid-phase peptide synthesis, and their modular design paired with the available repertoire of natural and non-natural amino acids allows for facile diversification of functional groups, and thus the resulting catalytic activities and substrate specificities of the peptide shell.…”

“…The conjunction of peptides and Au-NPs leads to dense peptide monolayers in which new hydrogen bond and/or charge interactions between individual peptides are established. This enables known enzyme-like effects, such as the perturbation of pK a values of functional groups and cooperativity in substrate binding [9,11], and can even lead to new catalytic mechanisms [7,8]. Altogether, these effects can greatly improve the catalytic performance of a conjugated versus an unconjugated peptide.…”

“…To date, the design and application of Pep-Au-NPs have been limited to organic esterase chemistry, in which catalysis is mediated by a His-imidazole [7][8][9][10][11]. Considering the fact that zinc metalloenzymes perform numerous other types of reactions in nature, including phosphodiester and amide hydrolysis as well as the (de)hydrogenation of alcohols [12,13], it is of great interest to reconstitute such transformations in vitro by developing appropriate robust synthetic systems.…”