The interactions of tetrakis(4-N-methylpyridyl)-porphine (H2TMpyP-4) and its copper(II), nickel(II), zinc(II), cobalt(III), iron(III), and manganese(III) derivatives with several nucleic acids have been investigated. Spectrophotometric titrations of H2TMpyP-4 and Cu(II)TMpyP-4 with the synthetic polymer poly(dG-dC) could be analyzed by a nearest-neighbor exclusion model leading to n approximately equal to two base pairs and equilibrium constants of 7.7 X 10(5) M-1 and 8.0 X 10(5) M-1, respectively. The other metal derivatives [except for the nickel(II) porphyrin] do not provide sufficiently large color changes with poly(dG-dC) to allow analysis. In contrast, all of these porphyrins interact with poly(dA-dT) and DNA. For those porphyrins investigated, the binding profiles are not adequately fit by a nearest-neighbor exclusion model but have profiles suggesting that cooperativity effects are important. Spectral and circular dichroic experiments both suggest base specificity. With calf thymus DNA, the copper(II) and nickel(II) derivatives show prominent negative circular dichroism (CD) features and large red shifts and hypochromicity of the Soret absorption band characteristic of GC specificity, as demonstrated with the synthetic polymer. The other metal derivatives show prominent positive induced visible CD features with small red shifts and hypochromicity of the absorption bands in the Soret region characteristic of AT specificity. Only the metal-free derivative has a conservative CD spectrum suggesting distribution among GC and AT sites.

Interactions of porphyrins with nucleic acids

II. DNA BINDING ANTIBIOTICS 1. Pyrrole-Amidine Antibiotics and Synthetic Analogues (a) Structure and physical properties (b) Interactions with nucleic acids and synthetic polynucleotides (i) Netropsin (ii) Interaction of distamycin A (iii) Interactions of distamycin analogues (iv) Bifunctional netropsin-like compounds (c) Interactions with deoxyolioomers (d) Sequence specificity and mode of interaction (e) Association constants and thermodynamic aspects (f) Geometry and dynamics 2. Mithramycin and Structural Analogues 3. Anthramycin, Sibiromycin and Related Antibiotics 4. Other Antitumour Antibiotics

Nonintercalating dna binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material

Reported studies indicate that the association of potassium monopersulfate with [Mn(TMPyP)](OAc)5, a water-soluble manganese porphyrin complex, leads to an efficient reagent for the oxidative cleavage of DNA. Single-strand breaks (SSBs) are observed on double-stranded DNA at manganese porphyrin concentrations as low as 0.5 nM with a short incubation time of 1 min. The number of SSBs linearly varies with the concentration of the manganese complex, and potassium monopersulfate is at least 3 orders of magnitude more efficient as oxygen source than hydrogen peroxide. Cleavage efficiency is optimal in the pH range 7.5-9.0 for a NaCl concentration between 80 and 150 mM or for a MgCl2 concentration of 10 mM. At very low manganese porphyrin concentration and by increasing the incubation time a catalytic cleavage activity of the complex is evidenced: up to 5 SSBs per manganese porphyrin are observed. The high cleavage activity of the monopersulfate-manganese porphyrin system makes it a good candidate for DNA-footprinting experiments.

Potassium monopersulfate and a water-soluble manganese porphyrin complex, [Mn(TMPyP)](OAc)5, as an efficient reagent for the oxidative cleavage of DNA.

Fluorescent dyes which are specific for duplex DNA have found a wide range of applications from staining gels to visualization of chromosomes. Porphyrin dyes have been found which are highly fluorescent in the presence of quadruplex but not duplex DNA. These dyes may offer a route to the specific detection of quadruplex DNA under biologically important conditions. There are three types of DNA quadruplex structures, and these may play important roles in telomere, centromere, triplet repeat, integration sites and other DNAs, and this first set of porphyrin dyes show some selectivity between the quadruplex types.

Fluorescent dyes specific for quadruplex DNA

Research involving three important interactions of synthetic cationic porphyrins with nucleic acids: DNA binding, oxidative-reductive strand scission and photosensitized strand scission, is examine...

Porphyrin—Nucleic Acid Interactions: A Review

The large meso-substituted porphine, meso-tetra(4-N-methylpyridyl)porphine has been identified as a DNA-interactive ligand with a capacity for intercalation (1,2). Subsequently, the 2-N-methyl, 3-N-methyl and N-trimethylanilinium analogues of this porphyrin intercalator have been obtained for physico-chemical analyses (absorption spectroscopy, viscometry, circular dichroism, unwinding of supercoiled DNA). In this paper we discuss the factors affecting the character of porphyrin binding (intercalative, as is the case for the 4-N-methyl and 3-N-methyl porphines, versus non-intercalative, as is the case for the 2-N-methyl and N-trimethylanilinium porphines) and the impact that porphyrins' binding has upon the structure of DNA. The molecular conformation of the porphyrin ligand varies slightly within this series so that the ability of a given porphyrin to intercalate may be correlated with the arrangement of charged groups, the planarity of the porphine ring and the effective width of the individual molecules. The results from these studies indicate that sequence selective binding occurs within a small aperture of solution conditions.

Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA

Circular dichroism spectroscopy of a cationic porphyrin bound to DNA.

The interactions of two positional isomers and one analogue of meso-tetra (4-N-methylpyridyl) porphine, with the synthetic polynucleotides poly[d(A-T)]  poly[d(A-T)] and poly[d(G-C)]  poly[d(G-C)] have been investigated by circular dichroism All four porphyrins were found to bind to the polynucleotides as shown by the induction of circular dichroism in their Soret bands Furthermore, the sign of the induced ellipticity reflects selective occupation of binding sites by the porphyrin ligands The conformational lability of poly[d(A-T)] X poly[d(A-T)] was found to be appreciable as micromolar amounts of meso-substituted 4-N-methylpyridyl, 3-N-methylpyridyl, and p-N-trimethylanilinium porphines induced a CD spectrum similar but not identical to that of DNA in the Z-form, ie a negative band at 280 nm and a positive band at 259 nm The effect of porphyrin binding to poly[d(G-C)] X poly[d(G-C)] was less pronounced and dissimilar to that seen in the AT polymer

Mark J. Carvlin

Papers

Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA

Circular dichroism spectroscopy of a cationic porphyrin bound to DNA.

Intercalative and nonintercalative binding of large cationic porphyrin ligands to polynucleotides

DNA interactive porphyrins: metalloporphyrin derivatives.