Factors Influencing the Activity of Nanozymes in the Cleavage of an RNA Model Substrate

Abstract

A series of 2-nm gold nanoparticles passivated with different thiols all featuring at least one triazacyclonanone-Zn(II) complex and different flanking units (a second Zn(II) complex, a triethyleneoxymethyl derivative or a guanidinium of arginine of a peptide) were prepared and studied for their efficiency in the cleavage of the RNA-model substrate 2-hydroxypropyl-p-nitrophenyl phosphate. The source of catalysis for each of them was elucidated from the kinetic analysis (Michaelis–Menten profiles, pH dependence and kinetic isotope effect). The data indicated that two different mechanisms were operative: One involving two Zn(II) complexes and the other one involving a single Zn(II) complex and a flanking guanidinium cation. The mechanism based on a dinuclear catalytic site appeared more efficient than the one based on the cooperativity between a metal complex and a guanidinium.

Hydrolytic Nanozymes

“…This appears to be true also for the gold nanoparticles . Second and third generations of these AuNPs (Figure ) showed how important the lipophilicity of the monolayer is and that cationic functional groups, like the guanidinium of Arg, may replace the second metal ion, although with lower efficiency . For monovalent substrates (i.e.…”

A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates

“…Although in modern life sciences gapmers [2,14,15] and siRNAs [16] are the preferred tools for achieving the site-specific cleavage of RNA strands, there is still interest in synthetic ribonucleases and recent years have seen important progress in the field. Effective catalysts that are based on metal ions [17][18][19][20][21][22][23], guanidines or polyamines [24][25][26][27], peptide conjugates [28][29][30][31][32], and deoxyribozymes [33,34] have been described. Starting from heterocyclic guanidine analogs [35], we have investigated the conjugates of tris(2-aminobenzimidazoles) and different types of oligonucleotides, such as DNA [36], PNA [37,38], or DNA-LNA mixmers [39], which were shown to act as sequence-specific metal-free RNA cleavers.…”

A Gold Nanoparticle Nanonuclease Relying on a Zn(II) Mononuclear Complex

“…[23] This is anon-existing option for TACN-Zn(II). [24,25] In this paper anew generation of AuNPs is studied where several functional groups and not just metal ions form the catalytic site of the nanozyme.W es how that cooperation between them in the confined space of an anoparticle passivating monolayer is possible.T his allowed us to obtain one of the most efficient DNA-cleaving Zn(II)-nanozymes reported so far.W ea lso show how evaluating ac atalyst against am odel substrate (as bis-p-nitrophenylphosphate, BNP,inthe case of DNA) may lead to wrong conclusions on its efficiency against the real biological target.…”