Specific and highly efficient condensation of GC and IC DNA by polyaza pyridinophane derivatives

Abstract

Two bis-polyaza pyridinophane derivatives and their monomeric reference compounds revealed strong interactions with ds-DNA and RNA. The bis-derivatives show a specific condensation of GC- and IC-DNA, which is almost two orders of magnitude more efficient than the well-known condensation agent spermine. The type of condensed DNA was identified as ψ-DNA, characterized by the exceptionally strong CD signals. At variance to the almost silent AT(U) polynucleotides, these strong CD signals allow the determination of GC-condensates at nanomolar nucleobase concentrations. Detailed thermodynamic characterisation by ITC reveals significant differences between the DNA binding of the bis-derivative compounds (enthalpy driven) and that of spermine and of their monomeric counterparts (entropy driven). Atomic force microscopy confirmed GC-DNA compaction by the bis-derivatives and the formation of toroid- and rod-like structures responsible for the ψ-type pattern in the CD spectra.

Novel Tripodal Polyamine Tris-Pyrene: DNA/RNA Binding and Photodynamic Antiproliferative Activity

“…Such a strong decrease of DNA/RNA CD spectra suggests almost a complete loss of double helix chirality, likely caused by the neutralisation of DNA/RNA negative charges by positively charged TAL3PYR and the consequent collapse of helical secondary structure. Here we did not observe appearance of the ψ-DNA, as we reported for the close analogue L2 ( Scheme 1 , [ 18 ]).…”

“…Interestingly, the much lower ds-RNA over ds-DNA selectivity observed for L5 in comparison to L2 was ascribed to the ability of phenanthroline to intercalate between the base pairs of the polynucleotides. These compounds condensed GC-DNA into ψ-DNA [ 18 ].…”

Recognition of ATT Triplex and DNA:RNA Hybrid Structures by Benzothiazole Ligands

“…Interestingly, compound 3, unlike its regioisomer 1, induced a strong increase in the intensity of CD spectra of ATT triplex, poly dA−poly dT, and ctDNA (ctDNA at 275 nm, AT-DNA at 260 and 282 nm, and ATT at 282 nm) compared to the intrinsic CD bands of these polynucleotides, and in addition, strong positive ICD bands located around 350 nm (Figure 9, Supplementary Materials). Similar strong changes in CD spectra of polynucleotides were noticed with bispolyaza pyridinophane derivatives that, similarly to compound 3, consist of two chains attached to pyridine as a central unit [66]. The reason that compound 3 induced condensation-like changes, while compound 1 did not, is probably the position of chains on the pyridine ring.…”

“…The mode of binding of 6 with the ATT triple structure suggested by the spectroscopic methods was consistent with the results obtained by molecular modeling. Similar strong changes in CD spectra of polynucleotides were noticed with bis-polyaza pyridinophane derivatives that, similarly to compound 3, consist of two chains attached to pyridine as a central unit [66]. The reason that compound 3 induced condensation-like changes, while compound 1 did not, is probably the position of chains on the pyridine ring.…”

Impact of the zinc complexation of polytopic polyaza ligands on the interaction with double and single stranded DNA/RNA and antimicrobial activity

“…23 In addition, we developed two polytopic polyaza ligands (PYPOD and PHENPOD, Scheme 1) and explored the zinc, 24 copper, 25,26 and manganese 23 coordination in addition to the interaction with duplex (ds) DNA/RNA. 27,28 Herein, we report the interaction of these ligands (see Scheme 1) and their mono-and polynuclear zinc metal complexes with the double and single stranded DNA/RNA by UV thermal, fluorescence emission and circular dichroism spectroscopies. The ligands form mono-, bi-and trinuclear complexes in solution according to potentiometry, photophysical and NMR studies.…”