Histidine-Based Lipopeptides Enhance Cleavage of Nucleic Acids: Interactions with DNA and Hydrolytic Properties.

Interaction studies and cleavage activity experiments were carried out between plasmid DNA and a series of histidine-based lipopeptides. Specific fluorescent probes (ethidium bromide, Hoechst 33342, and pyrene) were used to monitor intercalation, minor groove binding, and self-assembly of lipopeptides, respectively. Association between DNA and lipopeptides was thus evidenced, highlighting the importance of both histidine and hydrophobic tail in the interaction process.

EPR spectroelectrochemical investigation of guanine radical formation and environment effects.

Guanine radical detection was carried out by a new convenient and efficient method coupling electron paramagnetic resonance spectroscopy and indirect electrooxidation of guanine in different biological environments, from the free nucleotide to several types of DNA substrates. Compared to the widely used photoirradiation method, this method appeared more selective in the choice of the electrochemical mediator. Carried out in presence of a ruthenium mediator and PBN as spin trap, this method revealed two types of EPR spectra depending of the environment of the guanine radical.

Contact photoallergy to isothipendyl chlorhydrate.

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies.

Correlations between electrochemical behaviors and DNA photooxidative properties of non-steroïdal anti-inflammatory drugs and their photoproducts.

Alkali-labile lesion to DNA photosensitized, via an electron transfer mechanism, by three non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen, tiaprofenic acid and naproxen and their photoproducts during drug photolysis, was investigated using (32)P-end labelled synthetic oligonucleotide. These photooxidative damages were correlated with the photophysical and electrochemical properties of drugs, appearing as the photosensitizer PS. Photophysical studies provided the excited state energies of the photosensitizer while their redox potentials and the relative stabilities of the PS(-) radical-anions were determined by cyclic voltammetry.

DNA photo-oxidative damage hazard in transfection complexes.

Complexes of DNA with various cationic vectors have been largely used for nonviral transfection, and yet the photochemical stability of DNA in such complexes has never been considered. We studied, for the first time, the influence of DNA complexation by a cationic lipid and polymers on the amount of damage induced by benzophenone photosensitization. The localization of benzophenone inside the hydrophobic domains formed by a cationic lipid, DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride), and close to DNA, locally increases the photoinduced cleavage by the reactive oxygen species generated.

Modulation of photo-oxidative DNA damage by cationic surfactant complexation.

The natural packaging of DNA in the cell by histones provides a particular environment affecting its sensitivity to oxidative damage. In this work, we used the complexation of DNA by cationic surfactants to modulate the conformation, the dynamics, and the environment of the double helix. Photo-oxidative damage initiated by benzophenone as the photosensitizer on a plasmid DNA complexed by dodecyltrimethylammonium chloride (DTAC), tetradecyltrimethylammonium chloride (TTAC), cetyltrimethyammonium chloride (CTAC) and bromide (CTAB) was detected by agarose gel electrophoresis.

Photodistribution of blue-gray hyperpigmentation after amiodarone treatment: molecular characterization of amiodarone in the skin.

Background: For decades, the photodistributed blue-gray skin hyperpigmentation observed after amiodarone therapy was presumably attributed to dermal lipofuscinosis. Using electron microscopy and high-performance liquid chromatography, we identified amiodarone deposits in the hyperpigmented skin sample from a patient treated with this antiarrhythmic agent. Our findings therefore indicate that the hypothesis relating the blue-gray hyperpigmentation to lipofuscin should be challenged.

Comparative study of the photophysical properties of indoprofen photoproducts in relation with their DNA photosensitizing properties.

The photophysical properties of indoprofen photoproducts have been examined in various solvents by absorbance and emission spectroscopies in relation with their photosensitizing properties. The photophysical properties of 2-[4-(1-hydroxy)ethylphenyl]isoindolin-1-one (HOINP) and 2-(4-ethylphenyl)isoindolin-1-one (ETINP) are typical of a singlet excited state when the ones of 2-(4-acetylphenyl)isoindolin-1-one (KINP) are based on its triplet excited state according to previous work. The effect of solvent polarity on the absorption and fluorescence properties of HOINP and ETINP has been investigated as a function of Delta f, the Lippert solvent polarity parameter.

DNA photosensitization by indoprofen - is DNA damage photoinduced by indoprofen or by its photoproducts?

The in vitro photosensitizing activity of indoprofen, a non-steroidal anti-inflammatory drug, toward DNA has been studied by gel sequencing experiments using (32)P-end labelled synthetic oligonucleotides in phosphate buffered solution. Upon irradiation at [small lambda] > 320 nm, piperidine-sensitive lesions were induced in single- and double-stranded DNA, exclusively at the position of guanine bases. In single-stranded DNA, all G sites were modified.

Photochemical and photophysical properties of indoprofen.

The photophysical properties and photochemistry of indoprofen (INP) have been investigated. Absorption and emission spectroscopies in phosphate buffer, ethanol and ether show that INP photophysics is dominated by a singlet-singlet transition of pipi* character. INP fluoresces at room temperature, with a quantum yield approximately 0.

Comparison of DNA damage photoinduced by ketoprofen, fenofibric acid and benzophenone via electron and energy transfer.

Ketoprofen (KP) and fenofibrate, respectively, anti-inflammatory and hypolipidemiant agents, promote anormal photosensitivity in patients and may induce photoallergic cross-reactions correlated to their benzophenone-like structure. Here, their ability to photosensitize the degradation of biological targets was particularly investigated in DNA. The photosensitization of DNA damage by KP and fenofibric acid (FB), the main metabolite of fenofibrate, and their parent compound, benzophenone (BZ), was examined on a 32P-end-labeled synthetic oligonucleotide in phosphate-buffered solution using gel sequencing experiments.

Photosensitivity to ketoprofen: mechanisms and pharmacoepidemiological data.

The topical use of nonsteroidal anti-inflammatory drugs (NSAIDs), widely used for moderate acute and chronic painful conditions, is one of several strategies used to improve the tolerability profile of NSAIDs, particularly with regard to gastric and renal adverse effects. However, topical NSAIDs can induce photosensitivity. Among the different NSAIDs used topically, ketoprofen has often been implicated in photosensitivity reactions.

Comparison of the DNA damage photoinduced by fenofibrate and ketoprofen, two phototoxic drugs of parent structure.

Fenofibrate and ketoprofen (KP) are two drugs of similar structure derived from that of benzophenone. Both are photoallergic and promote cross reactions in patients. However, the cutaneous photosensitizing properties of KP also include phototoxic effects and are more frequently mentioned.

Nonsteroidal antiinflammatory drug-photosensitized formation of pyrimidine dimer in DNA.

Phototoxic nonsteroidal antiinflammatory drugs (NSAIDs) may induce DNA damage in vitro upon irradiation. In this study, we investigated the ability of ketoprofen (KP), tiaprofenic acid (Tia), naproxen (NP) and indomethacin (IND) to photosensitize the formation of pyrimidine dimers and single strand breaks. Both kinds of damage were sought by analyzing DNA-drug mixtures irradiated at 313 nm by agarose gel electrophoresis.

Structural determination of a glucuronide conjugate of flucytosine in humans.

The structure of a glucuronide metabolite of flucytosine (FC; 5-fluorocytosine), found in the urine of all patients treated with this antifungal drug, was determined. This compound is the O2-beta-glucuronide of FC. Its structure was established after isolation from urine and by comparing its spectroscopic characteristics with those of three FC glucuronides previously synthesized.

A new approach to the study of ifosfamide metabolism by the analysis of human body fluids with 31P nuclear magnetic resonance spectroscopy.

[31P] nuclear magnetic resonance spectroscopy was used to analyze body fluids from patients treated with ifosfamide (IF). This technique, which requires no labeled drug, allows a direct study of the biological sample with no need for extraction or derivatization and a simultaneous detection and quantification of all the different phosphorated metabolites in a single analysis. In urine, isophosphoramide mustard was detected in addition to the already known human urinary compounds [i.

Study of the metabolism of flucytosine in Aspergillus species by 19F nuclear magnetic resonance spectroscopy.

The metabolism of flucytosine (5FC) in two Aspergillus species (Aspergillus fumigatus and A. niger) was investigated by 19F nuclear magnetic resonance spectroscopy. In intact mycelia, 5FC was found to be deaminated to 5-fluorouracil and then transformed into fluoronucleotides; the catabolite alpha-fluoro-beta-alanine was also detected in A.