DNAzymes for amine and peptide lysine acylation

Abstract

DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However, finding DNAzymes for peptide lysine acylation is a substantial...

Defining the substrate scope of DNAzyme catalysis for reductive amination with aliphatic amines

“…These findings establish an experimental limit on the substrate scope of DNAzyme catalysis for reductive amination with aliphatic amines, likely originating in the difficulty of binding the less structurally organized amine substrates. For comparison, our recent work with analogous DNAzymes for amine acylation did lead to peptide acylation (e.g., with DNA-HEG-AAAKAA), 17 and therefore the feasi-…”

“…For comparison, our recent work with analogous DNAzymes for amine acylation did lead to peptide acylation ( e.g. , with DNA-HEG-AAAKAA), 17 and therefore the feasibility of DNAzyme catalysis depends on the type of chemical reaction and not solely the substrate. Our earlier study of Lys modification in another context showed that substrate reactivity can be more important than structural organization, 29 which is the opposite of our findings here.…”

“…[9][10][11][12][13] We have sought to expand DNAzyme catalysis to many reactions, including those relevant to peptide modification [14][15][16] such as amine acylation. 17 Another such reaction is amine alkylation, where the lysine (Lys) side chain is naturally methylated in many biologically relevant contexts, 18,19 and site-selective Lys alkylation is useful for introducing biochemical and biophysical probes. [20][21][22][23] Because Lys has an aliphatic amine side chain, here we assessed the ability to identify DNAzymes that engage various kinds of aliphatic amines in alkylation reactions.…”

DNAzyme‐Catalyzed Site‐Specific N‐Acylation of DNA Oligonucleotide Nucleobases

“…[13] We considered our recent effort in which DNAzyme-catalyzed N-acylation of aliphatic amine nucleophiles (e.g., lysine) was achieved using phenyl ester (PE) and 4-fluorophenyl ester (4FPE) electrophiles, whereas the background reactivity of 2,3,5,6-tetrafluorophenyl ester (TFPE; Figure 1A) was too high to allow any rate enhancement. [14] Here, with the less reactive exocyclic aromatic amine nucleophiles N 4 of C, N 2 of G, and N 6 of A (Figure 1B), we surmised that the more reactive TFPE electrophile may be appropriate as the acyl donor. We therefore performed new in vitro selection experiments in which DNA nucleobases have the amine nucleophiles and TFPE is the acyl donor.…”

Dual‐mode biosensing platform for ultrasensitive Salmonella detection based on cascaded signal amplification coupled with DNA‐functionalized Ag2S NPs@PB

“…Multicomponent nucleic acid enzyme (MNAzyme), a functional nucleic acid enzyme, is composed of a target arm, a reaction arm, and two partzymes (Yang & Chaput, 2021; Yin et al., 2021). MNAzyme with an intact catalytic core capable of cleaving multiple substrates can be activated by the input of any specific nucleic acid to generate an amplified output, which can inherently act as a universal amplification tool (Cozma et al., 2021; Yao et al., 2021). Given the characteristics of RCA products, a strategy combining RCA with MNAzyme is rationally designed in this study for the ultrasensitive detection of Salmonella through cascade signal amplification.…”