A red light-triggered chemical tool for sequence-specific alkylation of G-quadruplex and I-motif DNA.

The importance of non-canonical DNA structures such as G-quadruplexes (G4) and intercalating-motifs (iMs) in the fine regulation of a variety of cellular processes has been recently demonstrated. As the crucial roles of these structures are being unravelled, it is becoming more and more important to develop tools that allow targeting these structures with the highest possible specificity. While targeting methodologies have been reported for G4s, this is not the case for iMs, as evidenced by the limited number of specific ligands able to bind the latter and the total absence of selective alkylating agents for their covalent targeting. Furthermore, strategies for the sequence-specific covalent targeting of G4s and iMs have not been reported thus far. Herein, we describe a simple methodology to achieve sequence-specific covalent targeting of G4 and iM DNA structures based on the combination of (i) a peptide nucleic acid (PNA) recognizing a specific sequence of interest, (ii) a pro-reactive moiety enabling a controlled alkylation reaction, and (iii) a G4 or iM ligand orienting the alkylating warhead to the reactive residues. This multi-component system allows for the targeting of specific G4 or iM sequences of interest in the presence of competing DNA sequences and under biologically relevant conditions.

Ultrasound-promoted synthesis of novel bipodal and tripodalpiperidin-4-ones and silica chloride mediated conversion to its piperidin-4-ols: synthesis and structural confinements.

The ultrasound-promoted synthesis of novel bipodal and tripodalpiperidin-4-ones was carried out by the reaction of 4-piperidone hydrochloride monohydrate with different alkylating and acylating agents. It was preferably reduced to respective piperidin-4-ols by ultrasonic irradiation using silica chloride, which maintains higher yields by acting as an effective supporting polymer. The sterically hindered phthaloyl derivative of piperidin-4-one was synthesized by ultrasonic irradiation which was difficult by conventional methods.

Comparison of N-nitrosodiethylamine degradation in water by UV irradiation and UV/O3: efficiency, product and mechanism.

N-nitrosodiethylamine (NDEA) is a member of nitrosamines, which is strong carcinogenic. In order to explore an effective treatment method for NDEA removal from water, sole UV irradiation and UV/O(3) were carried out in this study. The removal efficiency, degradation products and pathways were compared between those two processes. Results showed that NDEA removal efficiency achieved 99% within 15 min by both UV and UV/O(3). Degradation reaction well followed pseudo-first-order kinetics. Water pH had different effect on NDEA degradation in those two processes. Acidic and neutral conditions were good for NDEA degradation by sole UV irradiation. However, NDEA underwent rapid degradation under various pH conditions in the UV/O(3) process. Though the ozone introduction in the UV/O(3) process had little effect on NDEA degradation efficiency, it had significant effect on its degradation products and pathways. Methylamine, dimethylamine, ethylamine and diethylamine were observed as aliphatic amine products of NDEA degradation in both two processes. They were assumed to arise due to N-N bond fission under UV irradiation, or due to the reaction of NDEA and hydroxyl radicals in the UV/O(3) process.

Ebola virus inactivation with preservation of antigenic and structural integrity by a photoinducible alkylating agent.

Current methods for inactivating filoviruses are limited to high doses of irradiation or formalin treatment, which may cause structural perturbations that are reflected by poor immunogenicity. In this report, we describe a novel inactivation technique for Zaire Ebola virus (ZEBOV) that uses the photoinduced alkylating probe 1,5-iodonaphthylazide (INA). INA is incorporated into lipid bilayers and, when activated by ultraviolet irradiation, alkylates the proteins therein. INA treatment of ZEBOV resulted in the complete loss of infectivity in cells. Results of electron microscopy and virus-capture assays suggested the preservation of conformational surface epitopes. Challenge with 50,000 pfu of INA-inactivated, mouse-adapted ZEBOV did not cause disease or death in mice. A single vaccination with INA-inactivated ZEBOV (equivalent to 5 x 10(4) pfu) protected mice against lethal challenge with 1000 pfu of ZEBOV. INA-inactivated virus induced a protective response in 100% of mice when administered 3 days before challenge. Thus, INA may have significant potential for the development of vaccines and immunotherapeutics for filoviruses and other enveloped viruses.