Molecular methods for assessment of non-covalent metallodrug–DNA interactions

Kellett, Andrew; Molphy, Zara; Slator, Creina; McKee, Vickie; Farrell, Nicholas

doi:10.1039/c8cs00157j

Cited by 220 publications

(163 citation statements)

References 52 publications

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“…We then chose EtBr to illuminate the serum-treated bc-apt and linear aptamers in agarose gel for further stability analysis. Since EtBr inserted itself into stacking bases of DNA, 48 it is easier for EtBr to illuminate the base pairing in DNA. Therefore, the bc-apt with 13 base pairings in the middle has the highest band intensity and then the band intensity of the bc-apt gradually decreased over hours which indicated that the stacking bases dissociating from each other over hours possibly resulted from serum nuclease.…”

Section: Resultsmentioning

confidence: 99%

A bispecific circular aptamer tethering a built-in universal molecular tag for functional protein delivery

Pan

Yang

et al. 2020

Chem. Sci.

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Section: Resultsmentioning

confidence: 99%

A bispecific circular aptamer tethering a built-in universal molecular tag for functional protein delivery

Pan

Yang

et al. 2020

Chem. Sci.

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“…Functional oligodeoxynucleotides (ODNs) have been widely designed for application in gene therapy, gene manipulation, diagnostics, and DNA‐type sensing devices for biomolecules in living cells . However, ODNs show limited cellular uptake and stability in cells; thus, efficient ODN delivery systems into cells with the aid of, for example, transfection reagents or microinjection techniques have been studied …”

Section: Methodsmentioning

confidence: 99%

Hybridizing Oligonucleotides with Hydrophobic Peptide Nucleic Acids Assists Their Cellular Uptake through Aggregate Formation

et al. 2020

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We appliedh ybridization between hydrophobic peptiden ucleic acids (PNAs) and oligodeoxynucleotides (ODNs) to achieve their cellular uptake without any need for transfection reagents. We employed ap yrenyl unit as ah ydrophobicf unctional group and introduced it at the terminus of the PNA strand.T he pyrene-tethered PNA (PyPNA)s trongly bound with its complementary ODNs to generate amphiphiles;t he resulting hybrids formed aggregates that showede fficient cellular uptake and high biological stability.A ggregatesc ontaining a functional DNA aptamer that bound to the PyPNA penetrated the cell membrane smoothly,w ith the aptamer exerting its originalf unction in living cells. Thus, PyPNA efficientlya ssisted the additive-free cellular uptake of ODNs.Functional oligodeoxynucleotides( ODNs) have been widely designed for applicationi ng ene therapy,g ene manipulation, diagnostics, and DNA-types ensing devices for biomolecules in living cells. [1][2][3][4][5][6] However,O DNs showl imited cellular uptake and stabilityi nc ells; [7] thus, efficient ODN delivery systems into cells with the aid of, for example, transfection reagents or microinjection techniquesh ave been studied. [8][9][10][11][12][13] One of the most useful methods for achieving efficient cellular uptake of ODNs is the use of modified ODNs. [14][15][16][17][18][19][20][21][22][23][24] ODNs conjugated with hydrophobic motifs, receptor ligands, or nanosized particles have all been efficientlyt aken up by cells. In addition, our group reported that ODNs bearing hydrophobic substituents formed aggregates that were easily transferred into cells through scavenger-receptor-mediatede ndocytosis withoutt he need for use of any additives. [22][23][24] Although these modifiedO DNs werev aluable fori ntake of ODNs into the cells, each ODN required individuals ynthesis. This synthesis complication has until now remained unsolved.Peptiden ucleic acids (PNAs) are artificial nucleic acidst hat recognize their complementary ODNs in as equence-specific manner. [25][26][27] In aP NA structure the hydrophilic phosphate backbone of DNA is replaced by ah ydrophobic peptideb ackbone, so PNAs are more hydrophobic than their DNA counterparts. We expected that the PNA could construct DNA amphiphiles due to hybridization.I na ddition, aP NA·DNA hybrid is thermodynamically more stable than the corresponding DNA duplex,a nd the modification of aPNA with functional substituents is relativelye asy.I nl ight of these unique properties, we designed aP NA bearingafunctional unit at the strand end, and hybridized it with ordinary DNA, leadingt ot he formation of an amphiphilic DNA·PNA hybrid.I nt his study,w ee mployed an aromatic pyrenyl motif as the hydrophobic substituent to enhancet he hydrophobicity of PNA and incorporated it into a PNA oligomer to give PyPNA (Scheme 1). In aqueous solution, the PyPNA·ODN hybrids formed aggregates that showed efficient cellular uptake. AT hT-binding DNA aptamer [28] also formed aggregates through hybridization with PyPNAa nd penetrated the cell membra...

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“…It has therefore since its inception been a key technique for inorganic chemists, and has gone from being an inherently complex and intellectually demanding technique to being an extremely efficient, cost-effective and routine technique since the double helix was first proposed. 1 Initially DNA may be viewed as an 'organic' molecule, and its base pairing abilities lead to the double helix structure first proposed by Crick and Watson using the X-ray diffraction data of Franklin and Wilkins. It also has a phosphate backbone which plays a very important role in the determining its chemical and physiological properties.…”

Section: Introduction 11 Dna Is the Biggest Ligandmentioning

confidence: 99%

Interactions Between Metal Ions and DNA

Cardin

2019

The Periodic Table II

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84 years elapsed between the announcements of the Periodic Table and that of the DNA double helix in 1953, and the two have been combined in many ways since then. In this chapter an outline of the fundamentals of DNA structure leads into a range of examples showing how the natural magnesium and potassium ions found in nature can be substituted in a diversity of applications. The dynamic structures found in nature have been studied in the more controlled, but artificial environment of the DNA crystal using examples from sodium to platinum, and also in a range of DNA-binding metal complexes. While nmr is an essential technique for studying nucleic acid structure and conformation, most of our knowledge of metal ion binding has come from X-ray crystallography. These days the structures studied, and therefore also the diversity of metal binding, go beyond the double helix to triplexes, hairpin loops, junctions and quadruplexes, and the chapter describes briefly how these pieces fit into the DNA jigsaw. In a final section, the roles of metal cations in the crystallisation of new DNA structures are discussed, along with an introduction to the versatility of the Periodic Table of absorption edges for nucleic acid structure determination.

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Molecular methods for assessment of non-covalent metallodrug–DNA interactions

Abstract: Herein we provide an accessible account of molecular methods to probe inorganic–nucleic acid interactions. Techniques are described using copper(ii) and platinum(ii) complexes prepared in our laboratories.

Cited by 220 publications

References 52 publications

A bispecific circular aptamer tethering a built-in universal molecular tag for functional protein delivery

A bispecific circular aptamer tethering a built-in universal molecular tag for functional protein delivery

Hybridizing Oligonucleotides with Hydrophobic Peptide Nucleic Acids Assists Their Cellular Uptake through Aggregate Formation

Interactions Between Metal Ions and DNA

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