Molecular, functional and structural properties of the prolyl oligopeptidase of Trypanosoma cruzi (POP Tc80), which is required for parasite entry into mammalian cells.

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Thermal stability of interstitial and substitutional Mn in ferromagnetic (Ga,Mn)As

© 2019 American Physical Society. In (Ga,Mn)As, a model dilute magnetic semiconductor, the electric and magnetic properties are strongly influenced by the lattice sites occupied by the Mn atoms. In particular, the highest Curie temperatures are achieved upon thermal annealing in a narrow temperature window around 200°C, by promoting the diffusion of interstitial Mn towards the surface. In this work, we determined the thermal stability of both interstitial and substitutional Mn in ferromagnetic (Ga,Mn)As thin films, using the emission channeling technique. At a higher Mn concentration, the temperatures at which substitutional and interstitial Mn become mobile not only decrease, but also become closer to each other. These findings advance our understanding of self-compensation in (Ga,Mn)As by showing that the strong dependence of the Curie temperature on annealing temperature around 200°C is a consequence of balance between diffusion of interstitial Mn and segregation of substitutional Mn

Evidence of tetragonal distortion as the origin of the ferromagnetic ground state in γ-Fe nanoparticles

γ-Fe and related alloys are model systems of the coupling between structure and magnetism in solids. Since different electronic states (with different volumes and magnetic ordering states) are closely spaced in energy, small perturbations can alter which one is the actual ground state. Here, we demonstrate that the ferromagnetic state of γ-Fe nanoparticles is associated with a tetragonal distortion of the fcc structure. Combining a wide range of complementary experimental techniques, including low-temperature Mössbauer spectroscopy, advanced transmission electron microscopy, and synchrotron radiation techniques, we unambiguously identify the tetragonally distorted ferromagnetic ground state, with lattice parameters a=3.76(2)Å and c=3.50(2)Å, and a magnetic moment of 2.45(5) μB per Fe atom. Our findings indicate that the ferromagnetic order in nanostructured γ-Fe is generally associated with a tetragonal distortion. This observation motivates a theoretical reassessment of the electronic structure of γ-Fe taking tetragonal distortion into account.The authors thank the Fund for Scientific ResearchFlanders, the Concerted Research Action of the KU Leuven (GOA/14/007), the KU Leuven BOF (STRT/14/002), the Hercules Foundation, the Portuguese Foundation for Science and Technology (CERN/FIS-NUC/0004/2015), and the European Union Seventh Framework through ENSAR2 (European Nuclear Science and Applications Research, Project No. 654002), and SPIRIT (Support of Public and Industrial Research Using Ion Beam Technology, Contract No. 227012). We acknowledge the European Synchrotron Radiation Facility (ESRF) for providing beam time (experiments 26-01-1018, 26-01-1057, 20-02-728, HC-1850, HC-2208), as well as C. Baehtz, N. Boudet, and N. Blancand for support during the experiments. We acknowledge the ISOLDE-CERN facility for providing beam time (experiment IS580) and technical assistance. The authors (L.M.C.P., F.K.) acknowledge the facilities and the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Centre for Advanced Microscopy, Australian National University. We also acknowledge the contribution of Prof. Mark Ridgway (Australian National University), who passed away before the work was completed

Lead Optimization of Phthalazinone Phosphodiesterase Inhibitors as Novel Antitrypanosomal Compounds

Human African trypanosomiasis is causing thousands of deaths every year in the rural areas of Africa. In this manuscript we describe the optimization of a family of phtalazinone derivatives. Phosphodiesterases have emerged as attractive molecular targets for a novel treatment for a variety of neglected parasitic diseases. Compound 1 resulted in being a potent TbrPDEB1 inhibitor with interesting activity against T. brucei in a phenotypic screen. Derivative 1 was studied in an acute in vivo mouse disease model but unfortunately showed no efficacy due to low metabolic stability. We report structural modifications to achieve compounds with an improved metabolic stability while maintaining high potency against TbrPDEB1 and T. brucei. Compound 14 presented a good microsomal stability in mouse and human microsomes and provides a good starting point for future efforts

Synthesis of 1-(2,4-dideoxy-beta-D-erythro-hexopyranosyl)thymine and its incorporation into oligonucleotides

The synthesis of 1-(2,4-dideoxy-beta-D-erythro-hexopyranosyl)thymine, starting from the well known carbohydrate precursors 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (12 steps) or from tri-O-acetyl-D-glucal (11 steps) is described.status: publishe

Acyclic nucleosides: useful for antisense constructs or as universal analogues for degenerate positions ?

status: publishe

Synthesis of 2,4-dideoxy-beta-D-erythro-hexopyranosyl nucleosides

The synthesis of 1-(2,4-dideoxy-beta-D-erythro-hexopyranosyl)thymine (12)1 was accomplished using two different synthetic routes. It was obtained starting either from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose or from tri-O-acetyl-D-glucal. The other modified nucleosides, with either a cytosine, guanine, or adenine moiety, were synthesized using the second reaction scheme. Deoxygenation reactions were accomplished with the (2,4-dichlorophenoxy)thiocarbonyl derivatives generated in situ.status: publishe