Background and purpose:
Cancer is the primary cause of death in the world. Vanadium (IV), a metal ion
complex, has been proposed as an appropriate applicant for cancer treatment. In this study, the interaction of an oxidovanadium (IV) complex [VOL(bipy)] with salmon sperm DNA and bovine serum albumin (BSA) was investigated
through experimental and computational approaches Using the results of this experimental study, the mechanism as well
as the parameters related to the interaction of [VOL(bipy)] with DNA and BSA was determined.
Material and methods:
The kinetic DNA and BSA interaction with [VOL(bipy)] was determined using absorption
titration and fluorescence quenching, respectively. Moreover, the possible interactions was calculated by molecular
docking prediction with available software.
Results:
The binding constant (Kb) of the complex to DNA was calculated to be 2.34×104 M-1
, indicating a relatively
strong interaction between the complex and DNA. It was found that the V(IV) complex interacted with DNA through
groove binding mode followed by partial intercalation into the DNA helix. The Kb values obtained for [VOL(bipy)]-BSA
interaction were in the range of 1.07×103
-5.82×104 M-1
. The V(IV) complex was found to prefer domain I binding pocket
of BSA with the ΔGb value of -7.52 kcal/mol.
Conclusion:
Both experimental and computational studies confirm the interaction of the Vanadium complex with DNA
and BSA. The moderate affinity of [VOL(bipy)] to BSA indicates that this protein is a good candidate for transferring the
complex.
Although BRACO19 is a potent G-quadruplex binder, its potential for clinical usage is hindered by its low selectivity towards DNA G-quadruplex over duplex. High-resolution structures of BRACO19 in complex with neither single-stranded telomeric DNA G-quadruplexes nor B-DNA duplex are available. In this study, the binding pathway of BRACO19 was probed by 27.5 µs molecular dynamics binding simulations with a free ligand (BRACO19) to a DNA duplex and three different topological folds of the human telomeric DNA G-quadruplex (parallel, anti-parallel and hybrid). The most stable binding modes were identified as end stacking and groove binding for the DNA G-quadruplexes and duplex, respectively. Among the three G-quadruplex topologies, the MM-GBSA binding energy analysis suggested that BRACO19′s binding to the parallel scaffold was most energetically favorable. The two lines of conflicting evidence plus our binding energy data suggest conformation-selection mechanism: the relative population shift of three scaffolds upon BRACO19 binding (i.e., an increase of population of parallel scaffold, a decrease of populations of antiparallel and/or hybrid scaffold). This hypothesis appears to be consistent with the fact that BRACO19 was specifically designed based on the structural requirements of the parallel scaffold and has since proven effective against a variety of cancer cell lines as well as toward a number of scaffolds. In addition, this binding mode is only slightly more favorable than BRACO19s binding to the duplex, explaining the low binding selectivity of BRACO19 to G-quadruplexes over duplex DNA. Our detailed analysis suggests that BRACO19′s groove binding mode may not be stable enough to maintain a prolonged binding event and that the groove binding mode may function as an intermediate state preceding a more energetically favorable end stacking pose; base flipping played an important role in enhancing binding interactions, an integral feature of an induced fit binding mechanism.
The interaction of water soluble meso-tetra-(4N-oxyethylpyridyl) porphyrin (TOEPyP4) and its Cu(II)- and Co(II)-containing derivatives (CuTOEPyP4 and CoTOEPyP4) with A and B forms of DNA at low ionic strength was studied via UV-vis spectrophotometry and Circular Dichroism. It is shown that the binding constant of TOEPyP4 and CuTOEPyP4 with A–DNA is two times larger than with B–DNA, and the binding constant of CoTOEPyP4 does not depend on the form of DNA. The thermodynamical analysis based on spectral data indicates the preferable entropic character of porphyrins binding with both forms of DNA. This result shows that at low ionic strength the external groove binding mode is a preferred binding mechanism of these porphyrins with both forms of DNA.
The first oxidative cleavage of DNA by manganese [Formula: see text]-confused porphyrin [chloro(2-aza-2-methyl-5,10,15,20-tetrakis([Formula: see text]-chlorophenyl)-21-carbaporphyrin)manganese(III), 1] using H2O2 as oxidant agent and its magnetic, calf thymus DNA(ct-DNA)- and human serum albumin (HSA) binding properties were investigated. The magnitude of the axial (D) zero-field splitting for the mononuclear Mn(III) center in 1 was determined to be approximately 2.71 cm[Formula: see text] by paramagnetic susceptibility measurements. The DNA- and HSA binding experimental results showed that 1 bound to ct-DNA via an outside groove binding mode and the hydrophobic cavity located in subdomain IIA of HSA with the binding constant of 4.144 × 105 M[Formula: see text] and [Formula: see text] 106 M[Formula: see text], respectively. Thermodynamic parameters revealed that both DNA- and HSA binding were spontaneous process. The main driven forces were the hydrogen bond and van der Waals for the former, but hydrophobic interaction for the latter, which were further confirmed by molecular docking modeling. Manganese [Formula: see text]-confused porphyrin 1 could cleave the supercoiled plasmid DNA efficiently in the presence of hydrogen peroxide. Hydroxyl radical ([Formula: see text]OH) was found the active species for oxidative damage of DNA.
A new series complexes of Ln nitrate with H2L, where Ln stands for La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, and H2L is 2-carboxybenzaldehyde- (4-hydroxy) benzoylhydrazone, were synthesized. Elemental analysis and IR spectroscopy were used to characterize and found that the complexes were Ln (HL)2(NO3)·4EtOH·4H2O type. The binding mode of complexes with CTDNA was investigated by UV-Vis titration and emission titration, suggesting that the complexes bind with CTDNA in a non-covalent groove binding mode.
Interactions of cationic tetrakis (N, N′, N″, N‴- tetramethyltetra-3, 4-pyridinoporphyrazinatozinc (II) (Zn (tmtppa)) with synthetic polynucleotides, poly (G-C) and poly (A-T), and calf thymus DNA have been characterized in 7.5 mM phosphate buffer of pH 7.2 by UV-Vis absorption and fluorescence spectroscopy. The appearance of hypochromicity more than 30% in UV-Vis spectra of porphyrazine due to interaction of both poly (G-C) and poly (A-T) indicates interaction similar to that of porphyrazine with DNA.The binding constants were determined from the changes in the Q-band maximum of the porphyrazine spectra at various poly (G-C) and DNA concentrations. The values of K were 2.5 × 106M−1, 2.5 × 106M−1and 2.5 × 105M−1for poly (G-C), poly (A-T) and DNA, respectively, at 25°C. The thermodynamic parameters (ΔG°, ΔH°, ΔS°) were calculated using the van't Hoff equation at various temperatures. The enthalpy and entropy changes were determined to be 41.14 kJ mol−1and 260.50 J mol−1·K−1for poly (G-C) and 53.59 kJ mol−1and 285.46 J mol−1·K−1for DNA at 25°C. The positive and large values of the entropy and enthalpy suggest that both hydrophobic and electrostatic interactions may play an important role in the stabilization of the complex formation. The binding of polynucleotides to porphyrazine quenches fluorescence emission of ethidium bromide (EB), and the quenching process obeys linear Stern-Volmer relationship. The results reviled groove-binding mode of porphyrazine for both AT- and GC-rich polynucleotides of DNA.
Photophysical properties of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin ( TMpyP 4) and its metallocomplexes M (II) TMpy P4 ( M = Zn , Cu , Ni , Co ) bound to natural DNA and synthetic poly-, oligo- and mononucleotides are considered with a primary emphasis placed upon intermolecular interaction of the photoexcited porphyrins with the nearest environment. Quenching of the fluorescent S 1 (but not triplet T 1) state due to guanine to porphyrin electron transfer is observed for TMpyP 4 intercalated between GC base pairs of the double-strand helixes, whereas in the case of TMpyP 4 complexed with guanosine monophosphate (GMP) both S 1 and T 1 states of the porphyrin are quenched. Furthermore, a dependence of the efficiency of TMpyP 4 triplet state quenching by the dissolved molecular oxygen from air on the porphyrin localization enables one to readily distinguish porphyrin groove binding mode from intercalation. Excited states of the TMpyP 4 complexes with transition metals, in spite of their very short lifetimes, also interact with nucleic acid components by means of an axial ligand binding/release to/from the metal. A possible structure of the five-coordinate excited complex (“exciplex”) formed in case of CuTMpyP 4 groove binding to some single- and double-strand polynucleotides is discussed.
Binding of BRACO19 to a Telomeric G-Quadruplex DNA Probed by All-Atom Molecular Dynamics Simulations with Explicit Solvent