53 research outputs found
Non-Natural Linker Configuration in 2,6-Dipeptidyl-Anthraquinones Enhances the Inhibition of TAR RNA Binding/Annealing Activities by HIV-1 NC and Tat Proteins
The HIV-1 nucleocapsid (NC) protein represents an excellent molecular target for the development of antiretrovirals
by virtue of its well-characterized chaperone activities, which play pivotal roles in essential steps of the viral life cycle.
Our ongoing search for candidates able to impair NC binding/annealing activities led to the identification of peptidylanthraquinones
as a promising class of nucleic acid ligands. Seeking to elucidate the inhibition determinants and increase the
potency of this class of compounds, we have now explored the effects of chirality in the linker connecting the planar nucleus to
the basic side chains. We show here that the non-natural linker configuration imparted unexpected TAR RNA targeting
properties to the 2,6-peptidyl-anthraquinones and significantly enhanced their potency. Even if the new compounds were able to
interact directly with the NC protein, they manifested a consistently higher affinity for the TAR RNA substrate and their TARbinding
properties mirrored their ability to interfere with NC-TAR interactions. Based on these findings, we propose that the
viral Tat protein, sharing the same RNA substrate but acting in distinct phases of the viral life cycle, constitutes an additional
druggable target for this class of peptidyl-anthraquinones. The inhibition of Tat-TAR interaction for the test compounds
correlated again with their TAR-binding properties, while simultaneously failing to demonstrate any direct Tat-binding
capabilities. These considerations highlighted the importance of TAR RNA in the elucidation of their inhibition mechanism,
rather than direct protein inhibition. We have therefore identified anti-TAR compounds with dual in vitro inhibitory activity on
different viral proteins, demonstrating that it is possible to develop multitarget compounds capable of interfering with processes
mediated by the interactions of this essential RNA domain of HIV-1 genome with NC and Tat proteins
Aspetti epidemiologici della calcolosi di calcio in Italia: distribuzione dei fenotipi intermedi nella popolazione italiana
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Diferentes níveis protéicos na dieta de girinos de rã-touro (Lithobates catesbeianus) e seus efeitos sobre o tecido hepático
Are food-deceptive orchid species really functionally specialized for pollinators?
Food-deceptive orchid species have traditionally been considered pollination specialized to bees or butterflies. However, it is unclear to which concept of specialization this assumption is related; if to that of phenotypic specialization or of functional specialization. The main aim of this work was to verify if pollinators of five widespread food-deceptive orchid species (Anacamptis morio (L.) R.M. Bateman, Pridgeon & M.W. Chase, Anacamptis pyramidalis (L.) Rich., Himantoglossum adriaticum H. Baumann, Orchis purpurea Huds. and Orchis simia Lam.) predicted from the phenotypic point of view matched with the observed ones. We addressed the question by defining target orchids phenotypic specialization on the basis of their floral traits, and we compared the expected guilds of pollinators with the observed ones. Target orchid pollinators were collected by conducting a meta-analysis of the available literature and adding unpublished field observations, carried out in temperate dry grasslands in NE Italy. Pollinator species were subsequently grouped into guilds and differences in the guild spectra among orchid species grouped according to their phenotype were tested. In contradiction to expectations derived from the phenotypic point of view, food-deceptive orchid species were found to be highly functionally generalized for pollinators, and no differences in the pollinator guild spectra could be revealed among orchid groups. Our results may lead to reconsider food-deceptive orchid pollination ecology by revaluating the traditional equation orchid-pollination specialization
Adição ao tabaco e hipertensão arterial sistêmica em jovens mulheres: indicadores de prevalência a partir de um estudo caso-controle
Adição ao tabaco e hipertensão arterial sistêmica em jovens mulheres: indicadores de prevalência a partir de um estudo caso-controle
Desenvolvimento de um método de digitalização de imagens de refeições para estudo de comportamento alimentar
Desenvolvimento de um método de digitalização de imagens de refeições para estudo de comportamento alimentar
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