Issue 43, 2023

Co-assembly-mediated biosupramolecular catalysis: thermodynamic insights into nucleobase specific (oligo)nucleotide attachment and cleavage

Abstract

Gaining control over the stability and cleavage of phosphoester and phosphodiester remains a matter of interest for their application in biotechnology to oligonucleotide-based therapeutics. Herein, we report an efficient unactivated phosphoester hydrolysis (stable mono/di/tri/cyclic nucleotide to nucleoside conversion) via a biosupramolecular system comprising of a non-covalent complex of enzyme, alkaline phosphatase (ALP), and Zn(II)-metallosurfactant. We also demonstrate the nucleobase selective activation or inhibition of ALP-mediated oligonucleotide digestion process using that complex. The higher binding affinity of Zn(II)-containing headgroup with phosphate-containing substrate enhanced the effective substrate concentration surrounding the enzyme, which, in turn, results in a drastic decrease in the Michaelis constant (KM), along with an increase in the turnover (kcat). The catalytic activation or inhibition of nucleobase-specific oligonucleotide digestion depends on the hydration, localization of the substrates, and viscosity of the resultant co-assembly upon substrate binding with the enzyme-metallosurfactant complex. Additionally, through isothermal titration calorimetry experiment, we demonstrate enthalpy–entropy change during both the supramolecular binding of (oligo)nucleotides and simultaneous activation/inhibition in catalytic cleavage. Overall, it showed the possible modularity of Zn(II)-mediated biosupramolecular interaction, describing intrinsic thermodynamic aspects in developing complex biocatalytic circuits with nucleobase-specific oligonucleotides inputs, which are relevant in designing nucleic acid-based cargo for drug delivery and bioimaging.

Graphical abstract: Co-assembly-mediated biosupramolecular catalysis: thermodynamic insights into nucleobase specific (oligo)nucleotide attachment and cleavage

Supplementary files

Article information

Article type
Paper
Submitted
02 Aug 2023
Accepted
09 Oct 2023
First published
10 Oct 2023

J. Mater. Chem. B, 2023,11, 10383-10394

Co-assembly-mediated biosupramolecular catalysis: thermodynamic insights into nucleobase specific (oligo)nucleotide attachment and cleavage

Priyanka and S. Maiti, J. Mater. Chem. B, 2023, 11, 10383 DOI: 10.1039/D3TB01747H

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