A platinum–quinacridine hybrid as a G-quadruplex ligand

A novel platinum–quinacridine hybrid, comprising a monofunctional Pt moiety and a G-quadruplex ligand (mono-para-quinacridine or MPQ), has been synthesized and shown to interact with quadruplex DNA via a dual noncovalent/covalent binding mode. Denaturing gel electrophoresis was used to separate the various platination products of 22AG (an oligonucleotide that mimics the human telomeric repeat) by Pt-MPQ, and it was shown that two platinated adducts are highly stable quadruplex structures. Dimethylsulfate/piperidine treatment and 3′-exonuclease digestion of the isolated adducts allowed us to precisely determine the platination pattern of 22AG by Pt-MPQ, which displays three main sites G2, G10 and G22. Data presented herein support the hypothesis that Pt-MPQ traps preferentially the antiparallel structure of the 22AG quadruplex. Finally, the kinetics of Pt-MPQ platination using a construct containing both quadruplex DNA and a duplex DNA parts provide the first insights into the Pt-MPQ preference for quadruplex DNA over duplex DNA.     

A mobile agent model for fault-tolerant manipulation on distributed objects

In this paper, we discuss how to realize fault-tolerant applications on distributed objects. Servers supporting objects can be fault-tolerant by taking advantage of replication and checkpointing technologies. However, there is no discussion on how application programs being performed on clients are tolerant of clients faults. For example, servers might block in the two-phase commitment protocol due to the client fault. We newly discuss how to make application programs fault-tolerant by taking advantage of mobile agent technologies where a program can move from a computer to another computer in networks. An application program to be performed on a faulty computer can be performed on another operational computer by moving the program in the mobile agent model. In this paper, we discuss a transactional agent model where a reliable and efficient application for manipulating objects in multiple computers is realized in the mobile agent model. In the transactional agent model, only a small part of the application program named routing subagent moves around computers. A routing subagent autonomously finds a computer which to visit next. We discuss a hierarchical navigation map which computer should be visited price to another computer in a transactional agent. A routing subagent makes a decision on which computer visit for the hierarchical navigation map. Programs manipulating objects in a computer are loaded to the computer on arrival of the routing subagent in order to reduce the communication overhead. This part of the transactional agent is a manipulating subagent. The manipulation subagent still exists on the computer even after the routing subagent leaves the computer in order to hold objects until the commitment. We assume every computer may stop by fault while networks are reliable. There are kinds of faulty computers for a transactional agent; current, destination, and sibling computers where a transactional agent now exists, will move, and has visited, respectively. The types of faults are detected by neighbouring manipulation subagents by communicating with each other. If some of the manipulation subagents are faulty, the routing subagent has to be aborted. However, the routing subagent is still moving. We discuss how to efficiently deliver the abort message to the moving routing subagent. We evaluate the transactional agent model in terms of how long it takes to abort the routing subagent if some computer is faulty.

Genome-wide identification of antimicrobial peptides in the liver fluke,Clonorchis sinensis

The increase in prevalence of antimicrobial resistance makes the search for new antibiotic agents imperative. Antimicrobial peptides (AMPs) from natural resources have been recognized as suitable tools to combat antibiotic-resistant bacteria. The liver fluke Clonorchis sinensis living in germ-filled environments could be a good source of antimicrobials. Here, we report the use of a rational protocol that combines AMP predictions based on their physicochemical properties and their in vivo stability to discover AMP candidates from the entire genome of C. sinensis. To screen AMP candidates, in silico analyses based on the physicochemical properties of known AMPs, such as length, charge, isoelectric point, and in vitro and in vivo aggregation values were performed. To enhance their in vivo stability, proteins having proteolytic cleavage sites were excluded. As a consequence, four high-activity, highstability peptides were identified. These peptides could be potential starting materials for the development of new AMPs via structural modification and optimization. Thus, this study proposes a refined computational method to develop new AMPs and identifies four AMP candidates, which could serve as templates for further development of peptide antibiotics.     

Contribution of microwave accelerated distillation in the extraction of the essential oil of Zygophyllum album L.

Introduction – The aerial parts of Zygophyllum album L. are used in folk medicine as an antidiabetic agent and as a drug active against several pathologies. In this work we present the chemical composition of Algerian essential oils obtained by microwave accelerated distillation (MAD) extraction, a solventless method assisted by microwave. Objective – Under the same analytical conditions and using GC‐FID and GC‐MS, the chemical composition of the essential oil of Zygophyllum album L. extracted by MAD was compared with that achieved using hydrodistillation (HD). Methodology – The extracted compounds were hydrosoluble, and they were removed from the aqueous solution by a liquid extraction with an organic solvent. Results – Employing MAD (100°C, 30 min), the essential oil contained mainly oxygenated monoterpenes with major constituents: carvone and α‐terpineol. However, most of the compounds present in the hydrodistilled volatile fraction were not terpene species, with β‐damascenone as a major constituent. Conclusion – The MAD method appears to be more efficient than HD: after 30 min extraction time, the obtained yields (i.e. 0.002%) were comparable to those provided by HD after 3 h extraction. MAD seems to be more convenient since the volatile fraction is richer in oxygenated monoterpenes, species that are recognised for their olfactory value and their contribution to the fragrance of the essential oil. Copyright © 2010 John Wiley & Sons, Ltd.     

Mass rearing of Spalgis epius (Lepidoptera: Lycaenidae), a potential predator of mealybugs (Hemiptera: Pseudococcidae)

Spalgis epius (Lepidoptera: Lycaenidae) has been recorded as a potential predator of various species of mealybug crop pests worldwide. We describe the mass rearing of S. epius, as no information on this topic is available. Outdoor nylon tent cages of different dimensions were provided to achieve mating and oviposition as S. epius adults did not mate in the laboratory cages. Adults mated only in the tent cage (6×6×10 m) placed over a native tree (9 m height). The presence of a tree canopy inside the cage is essential to achieve courtship and mating. Gravid females of S. epius deposited eggs on the mealybug-infested pumpkins inside the different sized nylon cages with or without a bush/tree. Spalgis epius eggs were maintained on mealybug-infested pumpkins in the laboratory and developmental stages of the predator were reared. Adults fed on various diets laid significantly higher number of eggs than those of starved individuals. Spalgis epius with a life cycle completed in 21.2 days and 55.7 larvae, could be reared on a single mealybug-infested pumpkin.     

Design, synthesis and insight into the structure-activity relationship of 1,3-disubstituted indazoles as novel HIF-1 inhibitors

Design, synthesis and insight into the structure-activity relationship (SAR) of 1,3-disubstituted indazoles as novel HIF-1 inhibitors are described. In particular, the substituted furan moiety on indazole skeleton as well as its substitution pattern turns out crucial for the high HIF-1 inhibition.     

99mTc- and Re-labeled 6-dialkylamino-2-naphthylethylidene derivatives as imaging probes for β-amyloid plaques

Based on the conjugate strategy, two neutral ^99mTc labeled 2-(1-(6-(dialkylamino)naphthalen-2-yl)ethylidene)malononitrile (DDNP) and 1-(6-(dialkylamino)naphthalen-2-yl)ethanone (ENE) derivatives, and their corresponding rhenium complexes were synthesized. In vitro fluorescent staining indicated that the corresponding rhenium derivatives selectively stained the β-amyloid (Aβ) plaques in the brain sections of AD model mice with low background. Compared with FDDNP and FENE, the affinities of the corresponding rhenium derivatives to Aβ aggregates decreased about 10-14-fold. In vivo biodistribution experiments in normal mice showed that ^99mTc-MAMA-ENE displayed medium initial brain uptake (0.65 %ID/g at 2 min) with a reasonable washout from the brain (0.19 %ID/g at 2 h) while ^99mTc-MAMA-DDNP showed a low brain uptake (0.28 %ID/g at 2 min). Further optimize these ^99mTc-labeled tracers in order to improve their binding affinities to Aβ plaques and diffusion through the blood brain barrier may generate useful imaging agents for SPECT.     

Synthesis and spectroscopy of near infrared fluorescent dyes for investigating dichromic fluorescence

We developed a series of near infrared (NIR) cyanine dyes to study dichromic fluorescence phenomenon, which provides new protocols for in vivo optical imaging. Preliminary spectroscopic studies show that dichromic fluorescence correlates with structural symmetry. This feature suggests the potential use of dichromic fluorescent molecules to study biological processes that can alter the structural symmetry of the molecular probes.     

A new and efficient synthetic route for the anxiolytic agent CL285032

CL285032 is an anxiolytic compound currently under investigation as a possible treatment for canine noise phobia associated anxiety. A robust scale-up and manufacturing process is essential for the development and marketability of the drug. The current synthetic route, although reliable, requires seven steps and has a low overall yield (18%), leaving opportunity for improvement. We are presenting an efficient alternative approach toward the synthesis of CL285032 and the results thereof.