(E)-3-(4-Chloro­phen­yl)-3-[3-(4-chloro­phen­yl)-1H-pyrazol-1-yl]prop-2-enal

In the title compound, C18H12Cl2N2O, the pyrazole ring is almost planar [r.m.s. deviation = 0.002 Å] while the two chloro­phenyl rings are twisted out from the plane of the pyrazole ring, making dihedral angles of 5.3 (1) and 65.34 (4)°. In the crystal, centrosymmetric R 2 2(24) dimers are formed about crystallographic inversion centres through a pair of C—H⋯Cl inter­actions. These dimers are further linked through a C—H⋯O hydrogen bond, forming a C(8) chain extending along the a axis. C—H⋯π inter­actions are also observed

A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis

The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis . It is essential for the in vitro growth of M. tuberculosis and for survival of the bacteria in the mouse model of infection. PanC is absent from mammals. We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity. Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited growth of live M. tuberculosis in manner consistent with PanC inhibition. Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed

Priming with a Recombinant Pantothenate Auxotroph of Mycobacterium bovis BCG and Boosting with MVA Elicits HIV-1 Gag Specific CD8+ T Cells

A safe and effective HIV vaccine is required to significantly reduce the number of people becoming infected with HIV each year. In this study wild type Mycobacterium bovis BCG Pasteur and an attenuated pantothenate auxotroph strain (BCGΔpanCD) that is safe in SCID mice, have been compared as vaccine vectors for HIV-1 subtype C Gag. Genetically stable vaccines BCG[pHS400] (BCG-Gag) and BCGΔpanCD[pHS400] (BCGpan-Gag) were generated using the Pasteur strain of BCG, and a panothenate auxotroph of Pasteur respectively. Stability was achieved by the use of a codon optimised gag gene and deletion of the hsp60-lysA promoter-gene cassette from the episomal vector pCB119. In this vector expression of gag is driven by the mtrA promoter and the Gag protein is fused to the Mycobacterium tuberculosis 19 kDa signal sequence. Both BCG-Gag and BCGpan-Gag primed the immune system of BALB/c mice for a boost with a recombinant modified vaccinia virus Ankara expressing Gag (MVA-Gag). After the boost high frequencies of predominantly Gag-specific CD8+ T cells were detected when BCGpan-Gag was the prime in contrast to induction of predominantly Gag-specific CD4+ T cells when priming with BCG-Gag. The differing Gag-specific T-cell phenotype elicited by the prime-boost regimens may be related to the reduced inflammation observed with the pantothenate auxotroph strain compared to the parent strain. These features make BCGpan-Gag a more desirable HIV vaccine candidate than BCG-Gag. Although no Gag-specific cells could be detected after vaccination of BALB/c mice with either recombinant BCG vaccine alone, BCGpan-Gag protected mice against a surrogate vaccinia virus challenge

Los pronombres de la lengua toba con referencias a los del mocoví

Con motivo del hallazgo por el padre Pablo Hernández, S. J., del manuscrito que contiene la gramática y el vocabulario del idioma Mbayá, pedí al reverendo padre fray Zacarías Ducci, autor del valioso trabajo sobre los Indios Tacagalé y su lengua, que me obsequiase con un capí tulo ó capítulos suplementarios sobre los pronombres de tercera persona en éste y los demás idiomas afines, Toba, Mocoví y Abipón, con la intención de aumentar á la lista algo de lo que al respecto de los Mbayá nos ha dejado el padre Sánchez Labrador, que ha permanecido inédito, y aun desconocido en su mayor parte, por casi siglo y medio.El padre Ducci en el acto correspondió á mi invitación con el estudio á que estos párrafos sirven de prólogo, y hace tiempo que debió publicarse, cosa que no se ha realizado por inconvenientes que nunca faltan, por lo que pido al autor mil disculpas.Es indudable que tanto el Tacagalé del padre Ducci, O. F. M., como el Mbayá del padre Sánchez Labrador, S. J., son los dos trabajos más completos que poseemos de los idiomas del Chaco, tipo Guaycurú, y con este complemento que ahora nos ofrece el primero, sabemos á qué atenernos en cuanto á esos pronombres demostrativos del Toba que tan curiosamente diferencian su lenguaje según la postura ó situación de la persona de quien se habla. Algo parecido se desprendía de lo que el padre Tavolini y otros habían apuntado sobre el Mocoví, y Dobrizhoffer sobre el Abipón;  pero todo ello era fragmentario si lo comparamos con lo que ahora nos establece el padre Ducci

Total syntheses of (&#177;) cervinomycins A<SUB>1</SUB> and A<SUB>2</SUB>

Regiocontrolled total syntheses of cervinomycins A1 (1) and A2 (2) have been achieved from easily accessible 6-acetyl-2-bromo-1,4,-dimethoxynaphthalene (4)

12/10- and 11/13-Mixed Helices in <i>α</i>/γ- and <i>β</i>/γ-Hybrid Peptides Containing C-Linked Carbo-<i>γ</i>-amino Acids with Alternating <i>α</i>- and <i>β</i>-Amino Acids

New classes of α/γ- and β/γ-hybrid peptides have been synthesized with novel 12/10- and 11/13-mixed helical patterns, respectively. The α/γ-peptides were derived from the dipeptide repeats with alternating arrays of l-Ala and γ-Caa(l) (C-linked carbo-γ-amino acid from d-mannose), which generated a new 12/10-mixed helix, for the first time, without a β-amino acid. The β/γ-peptides made from an alternating arrangement of β-Caa(x) (C-linked carbo-β-amino acid) and γ-Caa(x) (C-linked carbo-γ-amino acid from d-xylose), on the other hand, resulted in an unprecedented 11/13-helix. The secondary structures in these peptides have been ascertained from detailed NMR studies, and CD spectroscopy and molecular dynamics investigations provided additional support for the structures derived

12/10- and 11/13-Mixed Helices in <i>α</i>/γ- and <i>β</i>/γ-Hybrid Peptides Containing C-Linked Carbo-<i>γ</i>-amino Acids with Alternating <i>α</i>- and <i>β</i>-Amino Acids

New classes of α/γ- and β/γ-hybrid peptides have been synthesized with novel 12/10- and 11/13-mixed helical patterns, respectively. The α/γ-peptides were derived from the dipeptide repeats with alternating arrays of l-Ala and γ-Caa(l) (C-linked carbo-γ-amino acid from d-mannose), which generated a new 12/10-mixed helix, for the first time, without a β-amino acid. The β/γ-peptides made from an alternating arrangement of β-Caa(x) (C-linked carbo-β-amino acid) and γ-Caa(x) (C-linked carbo-γ-amino acid from d-xylose), on the other hand, resulted in an unprecedented 11/13-helix. The secondary structures in these peptides have been ascertained from detailed NMR studies, and CD spectroscopy and molecular dynamics investigations provided additional support for the structures derived

12/10- and 11/13-Mixed Helices in <i>α</i>/γ- and <i>β</i>/γ-Hybrid Peptides Containing C-Linked Carbo-<i>γ</i>-amino Acids with Alternating <i>α</i>- and <i>β</i>-Amino Acids

New classes of α/γ- and β/γ-hybrid peptides have been synthesized with novel 12/10- and 11/13-mixed helical patterns, respectively. The α/γ-peptides were derived from the dipeptide repeats with alternating arrays of l-Ala and γ-Caa(l) (C-linked carbo-γ-amino acid from d-mannose), which generated a new 12/10-mixed helix, for the first time, without a β-amino acid. The β/γ-peptides made from an alternating arrangement of β-Caa(x) (C-linked carbo-β-amino acid) and γ-Caa(x) (C-linked carbo-γ-amino acid from d-xylose), on the other hand, resulted in an unprecedented 11/13-helix. The secondary structures in these peptides have been ascertained from detailed NMR studies, and CD spectroscopy and molecular dynamics investigations provided additional support for the structures derived