Interaction of Arsenic Trioxide As₂O₃with DNA and RNA

Abstract

Arsenic salts have been used for centuries to treat a variety of medical conditions ranging from infectious disease to cancer. More recently, trivalent arsenic trioxide was found to exhibit high antitumor activity towards hematological malignancies. Even though much is known about antitumor activity and DNA damage by As2O3, there has been no report on the interaction of arsenic trioxide with isolated DNA or RNA. Therefore, it was of interest to examine the interaction of As2O3 with DNA and RNA in aqueous solution at physiological pH. FTIR and UV-visible difference spectroscopic methods were used to characterize the nature of drug-DNA and drug-RNA interactions and to determine the As binding site, the binding constant, the sequence selectivity, the helix stability, and the biopolymer secondary structure in the As2O3-polynucleotide complexes in vitro. The FTIR spectroscopic studies were conducted with As2O3-polynucleotide (phosphate) ratios of 1/40, 1/20, 1/10, and 1/5, with a final DNA (P) or RNA (P) concentration of 6.25 mmol/l. Spectroscopic results showed As2O3 binds to DNA and RNA at G-C, A-T, and A-U bases, and no interaction with the backbone PO2 group. As2O3-DNA and -RNA adducts showed one type of binding with overall binding constant of K(As2O3-DNA) = 1.24 x 10(5) M(-1) and K(As2O3-RNA) = 2.60 x 10(5) M(-1). The As2O3-polynucleotide complexation is associated with a partial biopolymer aggregation and no major alterations of B-DNA or A-RNA structure.

KML001 Cytotoxic Activity Is Associated with Its Binding to Telomeric Sequences and Telomere Erosion in Prostate Cancer Cells

“…The detectable number of copies of hTERT amplified from mRNA by real-time PCR was significantly reduced at both IC 50 and IC 100 concentrations of sodium metaarsenite after 24 h, which is in line with what has been reported by others (9,17). Based on our telomerase/telomere protein, RNA and DNA data, and a recent literature report, the reduction of hTERT mRNA is likely due to the possibility of the binding of sodium metaarsenite to A-U bases in RNA (26).…”

“…On the other hand, double-stranded coding DNA will be repaired (22). Arsenic trioxide was also reported to interact with DNA and RNA at G-C, A-T, and A-U bases (26). To test whether the trivalent arsenic compound KML001 can bind to telomeric sequences, a possibility that could explain the hTERT displacement data, for example, in Fig.…”

The Use of MALDI-TOF-MS and In Silico Studies for Determination of Antimicrobial Peptides’ Affinity to Bacterial Cells

“…Bacterial membranes strongly bind peptide dimers onto their surface by "sinking" of the hydrophobic core segment into the membrane. The equilibrium concentration of the antimicrobial peptides can be derived from the peak intensities in the mass spectra using the double reciprocal plot [35,36] and the affinity binding constant (K). After in silico assays it was possible to conclude that amp-1 and amp-2 interestingly corroborated in vitro data, reinforcing the idea of affinity and helping to understand the possible interaction mode.…”

Characterization of Metal Ion-Nucleic Acid Interactions in Solution

“…FT-IR (Fourier-transform infrared) spectroscopy and Raman spectroscopy have been employed to semiquantitatively follow metal ion-induced conformational changes [13,179,180] and identify primary binding sites for a variety of metal ions in RNA and DNA [181][182][183][184][185][186][187]. By …”