Dynamic Regulation Of DNA/Peptides Assembly Structure And Catalytic Performance Of Mimic Enzyme

Natural enzymes catalyze biochemical transformations in superior catalytic efficiency and remarkable substrate specificity.The excellent catalytic repertoire of enzymes is attributed to the sophisticated chemical structures of their active sites.However,large-scale practical applications of natural enzymes are restricted due to their poor stability,difficulty in modification,and high costs of production.One viable solution is to reconstruction of enzymatic active site in an artificial system.In this paper,the following works are explored in this regard.Inspired by the arrangement of amino acid residues in the catalytic center of horseradish peroxidase.We designed the self-assembly of the lysinecontaining peptides with guanine-rich DNA and hemin to form peroxidasemimicking active sites and catalytic nanoparticles.The DNA strand self-folds into a G-quadruplex structure that provides a supramolecular scaffold and a potential axial ligand for hemin.The β-sheet forming capability of the lysinecontaining peptides is found to affect the catalytic synergy between the Gquadruplex DNA and the peptide.It is hypothesized that the β-sheet formation of the peptides results in the enrichment of the lysine residues,which distribute on the distal side of hemin to promote the formation of Compound I,like distal arginine residue in natural heme pocket.Incorporation of the histidine residues into the lysine-containing peptides further enhanced the hemin activities,indicating the cooperation between the lysine and histidine.Furthermore,the peptide/DNA/hemin complexes can be switched between active and inactive state by reversible formation and deformation of the DNA G-quadruplex,which was attributed to the peptides-promoted conformational changes of the DNA components.This work opens an avenue to mimic the catalytic residues and their spatial distribution in the natural enzymes,and shed light on the design of the smart biocatalysts that can respond to the environmental stimuli.In addition,DNA strand replacement reactions play a crucial role in DNA nanotechnology,but the long reaction time limits its further development.Most conformational changes of DNA in living organisms are accomplished with the assistance of enzymes,such as E1 hexameric helicase to dissociate DNA double strands.Inspired by this,we found that lysine-based peptides can significantly enhance the rate of DNA strand replacement reaction.This may be attributed to the hydrogen bonding and electrostatic interactions between lysine residues and DNA to facilitate the proximity of two DNA strands to each other.In addition,the peptide can also enhance the rate of hybridization reactions between complex DNA strands as well as the hybridization chain reactions(HCR).Such peptides,which are perfectly biocompatible without any biotoxicity,may provide a more efficient,more convenient,and safer path for the further application of DNA nanotechnology.