DNA Triple Helix Stabilization by Aminoglycoside Antibiotics

Aminoglycoside–Nucleic Acid Interactions: The Case for Neomycin

“…The remarkable ability of neomycin and other aminoglycosides to stabilize DNA, RNA, and hybrid triple helices has been reported and discussed above [113][114][115][116]. Neomycin has also been shown to induce the stabilization of hybrid duplexes as well as hybrid triple helices [113].…”

“…Neomycin selectively stabilizes DNA triplex without affecting the duplex [113][114][115][116]. Increasing the molar ratios of neomycin from 0-25 µM, r db (ratio drug [neomycin]/base triplet)=1.67, increases the triplex melting point by nearly 25°C, whereas the duplex is virtually unaffected (Fig.…”

“…Therefore, if the structure of the nucleic acid-binding drug is novel, the emergence of resistance is likely to be slower than for protein targets (barring any novel efflux pump mechanisms).Antisense/antigene therapy can offer a viable alternative in tackling such resistance mechanisms. Recent findings that aminoglycosides can stabilize DNA/RNA triplexes [114,115], hybrid duplexes [113], and that neomycin can even induce hybrid triplex formation [113] suggested that aminoglycoside-DNA conjugates could be effective models for targeting nucleic acids sequence specifically (via a hybrid duplex or triplex formation). Conjugation of an aminoglycoside to an ODN can assist in the following processes:…”

Molecular recognition of single‐stranded RNA: Neomycin binding to poly(A)

“…There is extensive evidence describing the ability of aminoglycosides (e.g. neomycin) to bind both duplex and triplex forms of DNA, in addition to quadruplex structures, DNA:RNA hybrids, and to some extent, single-stranded nucleic acids [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

A comparative binding study of BIV Tat peptide against its TAR RNA duplex, RNA–DNA heteroduplex and DNA duplex

“…10,11 In addition, RNA binders such as aminoglycoside antibiotics have been observed to enhance efficient triplex DNA formation. [12][13][14] However, these observations do not necessarily imply that the rules involved in DNA binding could simply be extended for predicting how RNA molecules interact with their binding ligands, and vice versa. In this letter, we report on how conformations of nucleic acid will affect their ligand binding properties.…”