The Mechanism of Cleavage of RNA Phosphodiesters by a Gold Nanoparticle Nanozyme

Abstract

The cleavage of uridine 3'-phosphodiesters bearing alcohols with pK a ranging from 7.14 to 14.5 catalyzed by AuNPs functionalized with 1,4,7-triazacyclononane-Zn(II) complexes has been studied to unravel the source of catalysis by these nanosystems (nanozymes). The results have been compared with those obtained with two Zn(II) dinuclear catalysts for which the mechanism is fairly understood. Binding to the Zn(II) ions by the substrate and the uracil of uridine was observed. The latter leads to inhibition of the process and formation of less productive binding complexes than in the absence of the nucleobase. The nanozyme operates with these substrates mostly via a nucleophilic mechanism with little stabilization of the pentacoordinated phosphorane and moderate assistance in leaving group departure. This is attributed to a decrease of binding strength of the substrate to the catalytic site in reaching the transition state due to an unfavorable binding mode with the uracil. The nanozyme favors substrates with better leaving groups than the less acidic ones.

Short peptide-based cross-β amyloids exploit dual residues for phosphoesterase like activity

“…S17 †). 37,38 Next, a substrate along with truncated peptide binding pockets (MD simulations, Fig. 3a-d) were used to investigate the underlying energetics in the catalytic systems by modelling the transition state (see the ESI for details †).…”

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

“…vi) Conjugation of metal complexes with bioactive molecules such as peptides, nucleotides, and vitamins as well as DNA binders to recognize specific targets and promote highly efficient catalytic reaction [92] , [93] , [94] , [95] , [96] , [97] , [98] , [99] . vii) Nanoformulation of metal complexes with nanoparticles (nano-nucleases) to obtain cooperative systems with enhanced nuclease-like activity [41] , [90] , [100] , [101] , [102] , [103] , [104] , [105] , [106] , [107] .…”

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“…20-fold (3.0 × 10 −5 M, see entry 3 of Table 1). 12 The study of cAMP siblings where the charge was increased up to −4 (see Fig. 1 and entries 5-7 of Table 1) showed that the dissociation constant decreased by more than two orders of magnitude by doubling the charge (from cAMP to AMP) but only by 5-fold with each subsequent charge increase (from AMP to ADP and, possibly, ATP) down to less than 1.8 × 10 −7 M (ADP and even less for ATP).…”