DNA minicircles as novel STAT3 decoy oligodeoxynucleotides endowed with anticancer activity in triple-negative breast cancer.

Decoy technology is a versatile and specific DNA oligonucleotide-based targeting strategy of pathogenic transcription factors (TFs). Chemical modifications of linear decoy oligonucleotides have been made to decrease nuclease sensitivity because of the presence of free ends but at the cost of new limitations that affect their use as therapeutic drugs. Although a short DNA minicircle is a phosphodiester nucleic acid without free ends, its potential therapeutic activity as a TF decoy oligonucleotide has not yet been investigated.

Unexpected Order-Disorder Transition in Diacetylene Alcohol Langmuir Films.

The phase diagram of the Langmuir film of diacetylene alcohol-henicosa-5,7-diyn-1-ol-is investigated by means of surface pressure versus surface area isotherms, Brewster angle microscopy, X-ray reflectivity, and grazing incident X-ray diffraction. Among the usual phases described in the generic phase diagram of small head group molecules, one observes an unexpected reversible transition from an ordered condensed phase to a disordered one upon increasing the surface pressure. We postulate that the origin of this unusual, unprecedented transition results from the competition between the interactions between the diacetylene blocks in the hydrophobic chain and the hydrogen bonds between head groups and water.

Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria.

Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed [1]. Nucleic acid-based antibiotics are a new type of antimicrobials.

Liposomes for PET and MR Imaging and for Dual Targeting (Magnetic Field/Glucose Moiety): Synthesis, Properties, and in Vivo Studies.

We describe the potentiality of a new liposomal formulation enabling positron emission tomography (PET) and magnetic resonance MR() imaging. The bimodality is achieved by coupling a Ga-based radiotracer on the bilayer of magnetic liposomes. In order to enhance the targeting properties obtained under a permanent magnetic field, a sugar moiety was added in the lipid formulation.

Production of DNA minicircles less than 250 base pairs through a novel concentrated DNA circularization assay enabling minicircle design with NF-κB inhibition activity.

Double-stranded DNA minicircles of less than 1000 bp in length have great interest in both fundamental research and therapeutic applications. Although minicircles have shown promising activity in gene therapy thanks to their good biostability and better intracellular trafficking, minicircles down to 250 bp in size have not yet been investigated from the test tube to the cell for lack of an efficient production method. Herein, we report a novel versatile plasmid-free method for the production of DNA minicircles comprising fewer than 250 bp.

Tailored stimuli-responsive interaction between particles adjusted by straightforward adsorption of mixed layers of Poly(lysine)-g-PEG and Poly(lysine)-g-PNIPAM on anionic beads.

We report a simple and versatile method to functionalize anionic colloid particles and control particle solubility. Poly(lysine)-based copolymers (PLL) grafted with polyethylene oxide (PLL-g-PEG) or poly(N-isopropylacrylamide) (PLL-g-PNIPAM) spontaneously adsorb on bare beads dispersed in aqueous solutions of the copolymers. The final composition of the mixed ad-layers formed (i.

Different affinity of nuclear factor-kappa B proteins to DNA modified by antitumor cisplatin and its clinically ineffective trans isomer.

Nuclear factor-kappa B (NF-кB) comprises a family of protein transcription factors that have a regulatory function in numerous cellular processes and are implicated in the cancer cell response to antineoplastic drugs, including cisplatin. We characterized the effects of DNA adducts of cisplatin and ineffective transplatin on the affinity of NF-кB proteins to their consensus DNA sequence (кB site). Although the кB site-NF-κB protein interaction was significantly perturbed by DNA adducts of cisplatin, transplatin adducts were markedly less effective both in cell-free media and in cellulo using a decoy strategy derivatized-approach.

Analysis of neutral lipids from microalgae by HPLC-ELSD and APCI-MS/MS.

A method was developed to analyze neutral lipids through the use of three triglycerides, four free fatty acids, six di- and four mono-glycerides standards by high performance liquid chromatography (HPLC) normal phase coupled with either with evaporative light scattering detector (ELSD) or with mass spectrometry (MS) operating in atmospheric pressure chemical ionization (APCI) mode. The method was applied to the determination of the neutral lipid fraction from a Botryococcus braunii race A (B. braunii) culture.

Reversible quenching of a chromophore luminescence by color transition of a polydiacetylene.

A new reactive diacetylene molecule has been synthesized, incorporating a strongly luminescent chromophore, tetrazine (Tz). It readily polymerizes into the blue polydiacetylene (PDA) form, quenching the Tz luminescence already at concentrations ≤1 %. The blue to red PDA transition is thermally induced in the solid state and the original strong Tz emission is restored.

RILES, a novel method for temporal analysis of the in vivo regulation of miRNA expression.

Novel methods are required to investigate the complexity of microRNA (miRNA) biology and particularly their dynamic regulation under physiopathological conditions. Herein, a novel plasmid-based RNAi-Inducible Luciferase Expression System (RILES) was engineered to monitor the activity of endogenous RNAi machinery. When RILES is transfected in a target cell, the miRNA of interest suppresses the expression of a transcriptional repressor and consequently switch-ON the expression of the luciferase reporter gene.

Electrofluorescence switching of tetrazine-modified TiO2 nanoparticles.

Highly fluorescent tetrazine-modified TiO2 nanoparticles were prepared by the reaction of triethoxysilane-appended chloroalkoxy tetrazine (ESTZ) with TiO2 nanoparticles through a condensation reaction between the surface hydroxyl groups of an electrode and the silane anchor group of ESTZ. The prepared electrodes were used as robust fluorescent layers for electrochemical fluorescence switching (electrofluorochromism) applications in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) as a charge balancing mediator. The stable charge balancing mediator, TEMPO, in the electrolyte was found to be essential to reduce the intrinsic electron transport resistance of TiO2 in order to achieve reversible electrofluorescence switching.

Interaction studies of muts and mutl with DNA containing the major cisplatin lesion and its mismatched counterpart under equilibrium and nonequilibrium conditions.

The DNA mismatch repair (MMR) system participates in cis-diamminedichloroplatinum (II) (cisplatin) cytotoxicity through signaling of cisplatin DNA lesions by yet unknown molecular mechanisms. It is thus of great interest to determine whether specialized function of MMR proteins could be associated with cisplatin DNA damage. The major cisplatin 1,2-d(GpG) intrastrand crosslink and compound lesions arising from misincorporation of a mispaired base opposite either platinated guanine of the 1,2-d(GpG) adduct are thought to be critical lesions for MMR signaling.

White fluorescence from core-shell silica nanoparticles.

Into the white: Encapsulation of a naphthalimide moiety in the core of silica nanoparticles afforded nanospheres with a strong green excimeric emission. Together with the blue emission of the monomeric naphthalimide and the yellow fluorescence of the tetrazine acceptor on the outer shell, the added contributions provide intense white fluorescence upon 330 nm UV excitation.

An extremely facile synthesis of furans, pyrroles, and thiophenes by the dehydrative cyclization of propargyl alcohols.

Furans, pyrroles, and thiophenes are efficiently prepared by gold-catalyzed dehydrative cyclizations of readily available, heteroatom-substituted propargylic alcohols. The reactions are rapid, high-yielding, and procedurally simple, giving essentially pure aromatic heterocycles in minutes under open-flask conditions with catalyst loadings as low as 0.05 mol %.

A homogeneous resonance energy transfer-based assay to monitor MutS/DNA interactions.

Probing the interactions of the DNA mismatch repair protein MutS with altered and damaged DNA is of great interest both for the understanding of the mismatch repair system function and for the development of tools to detect mutations. Here we describe a homogeneous time-resolved fluorescence (HTRF) assay to study the interactions of Escherichia coli MutS protein with various DNA substrates. First, we designed an indirect HTRF assay on a microtiter plate format and demonstrated its general applicability through the analysis of the interactions between MutS and mismatched DNA or DNA containing the most common lesion of the anticancer drug cisplatin.

Binding of mismatch repair protein MutS to mispaired DNA adducts of intercalating ruthenium(II) arene complexes.

The present study was performed to examine the affinity of Escherichia coli mismatch repair (MMR) protein MutS for DNA damaged by an intercalating compound. We examined the binding properties of this protein with various DNA substrates containing a single centrally located adduct of ruthenium(II) arene complexes [(eta(6)-arene)Ru(II)(en)Cl][PF(6)] [arene is tetrahydroanthracene (THA) or p-cymene (CYM); en is ethylenediamine]. These two complexes were chosen as representatives of two different classes of monofunctional ruthenium(II) arene compounds which differ in DNA-binding modes: one that involves combined coordination to G N7 along with noncovalent, hydrophobic interactions, such as partial arene intercalation (tricyclic-ring Ru-THA), and the other that binds to DNA only via coordination to G N7 and does not interact with double-helical DNA by intercalation (monoring Ru-CYM).

Apoptosis induction and DNA interstrand cross-link formation by cytotoxic trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2) : cross-linking between d(G) and complementary d(C) within oligonucleotide duplexes.

We have investigated the cytotoxic activity, the induction of apoptosis, and the interstrand cross-linking efficiency in the A2780cisR ovarian tumor cell line, after replacement of the two NH3 nonleaving groups in trans-[PtCl2(NH3)2] (trans-DDP) by dimethylamine and isopropylamine. The data show that trans-[PtCl2(NH(CH)2)(NHCH(CH3)2)] is able to circumvent resistance to cis-[PtCl2(NH3)2] (cis-DDP, cisplatin) in A2780cisR cells. In fact, trans-[PtCl2(NH(CH3)2)(NHCH(CH3)2)] shows a cytotoxic potency higher than that of cis-DDP and trans-DDP, with the mean IC50 values being 11, 58, and 300 microM, respectively.

Modulation of MutS ATP-dependent functional activities by DNA containing a cisplatin compound lesion (base damage and mismatch).

DNA damage-dependent signaling by the DNA mismatch repair (MMR) system is thought to mediate cytotoxicity of the anti-tumor drug cisplatin through molecular mechanisms that could differ from those required for normal mismatch repair. The present study investigated whether ATP-dependent biochemical properties of Escherichia coli MutS protein differ when the protein interacts with a DNA oligonucleotide containing a GT mismatch versus a unique site specifically placed cisplatin compound lesion, a cisplatin 1,2-d(GpG) intrastrand cross-link with a mispaired thymine opposite the 3' platinated guanine. MutS exhibited substantial affinity for this compound lesion in hydrolytic and in non-hydrolytic conditions of ATP, contrasting with the normal nucleotide inhibition effect of mispair binding.

Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells: importance of apoptotic pathways.

cis-diamminedichloroplatinum(II) (cisplatin) is among the most active antitumour agent used in human chemotherapy. The purpose of this review is to give an insight in several molecular mechanisms that mediate the sensitivity of cancer cells to this drug and to show how recent progress in our knowledge on some critical molecular events should lay the foundations of a more rational approach to anticancer drug design. Cisplatin is primarily considered as a DNA-damaging anticancer drug, mainly forming different types of bifunctional adducts in its reaction with cellular DNA.

Binding discrimination of MutS to a set of lesions and compound lesions (base damage and mismatch) reveals its potential role as a cisplatin-damaged DNA sensing protein.

The DNA mismatch repair (MMR) system plays a critical role in sensitizing both prokaryotic and eukaryotic cells to the clinically potent anticancer drug cisplatin. It is thought to mediate cytotoxicity through recognition of cisplatin DNA lesions. This drug generates a range of lesions that may also give rise to compound lesions resulting from the misincorporation of a base during translesion synthesis.

Supported metallocene catalysts by surface organometallic chemistry. Synthesis, characterization, and reactivity in ethylene polymerization of oxide-supported mono- and biscyclopentadienyl zirconium alkyl complexes: establishment of structure/reactivity relationships.

The reactions of CpZr(CH(3))(3), 1, and Cp(2)Zr(CH(3))(2), 2, with partially dehydroxylated silica, silica-alumina, and alumina surfaces have been carried out with careful identification of the resulting surface organometallic complexes in order to probe the relationship between catalyst structure and polymerization activity. The characterization of the supported complexes has been achieved in most cases by in situ infrared spectroscopy, surface microanalysis, qualitative and quantitative analysis of evolved gases during surface reactions with labeled surface, solid state (1)H and (13)C NMR using (13)C-enriched compounds, and EXAFS. 1 and 2 react with silica(500) and silica-alumina(500) by simple protonolysis of one Zr-Me bond by surface silanols with formation of a single well-defined neutral compound.

Interstrand cross-links of cisplatin induce striking distortions in DNA.

In the reaction between cellular DNA and cisplatin, different bifunctional adducts are formed including intrastrand and interstrand cross-links. The respective role of these lesions in the cytotoxicity of the drug is not yet elucidated. This paper deals with the current knowledge on cisplatin interstrand cross-links and presents results on the formation, stability and structure of these adducts.