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Buarque C.D.,Pontifical Catholic University of Rio de Janeiro | Salustiano E.J.,Institute Bioquimica Medica Leopoldo Of Meis | Fraga K.C.,Pontifical Catholic University of Rio de Janeiro | Alves B.R.M.,Pontifical Catholic University of Rio de Janeiro
European Journal of Medicinal Chemistry | Year: 2014

Aza-deoxi-pterocarpans (1) were synthesized through palladium-catalyzed aza-arylation of dihydronaphtalen, and showed antineoplastic effect on MDR leukemic cell lines (K562, Lucena-1 and FEPS). Compounds 1c-d were prepared to identify the pharmacophoric group responsible for the activity as well as compounds 2a-c were prepared to evaluate the structural requirements in the D-ring. LQB-223 (1b) is the most promising antileukemic agent since it was the most active on MDR cells without detectable toxicity to normal immune system cells. © 2014 Elsevier Ltd. All rights reserved.

Silva J.L.,Institute Bioquimica Medica Leopoldo Of Meis | Oliveira A.C.,Institute Bioquimica Medica Leopoldo Of Meis | Vieira T.C.R.G.,Institute Bioquimica Medica Leopoldo Of Meis | De Oliveira G.A.P.,Institute Bioquimica Medica Leopoldo Of Meis | And 2 more authors.
Chemical Reviews | Year: 2014

The application of pressure has opened important frontiers for understanding how polypeptides fold into highly structured conformations, how they interact with ligands and other proteins, and how they assemble into supramolecular structures such as viruses and amyloids. In proteins, pressure induces changes that range from small conformational effects, compressibility effects, and changes in populations of intermediate states to complete loss of native folding. Applying high pressure is also an excellent approach for studying situations in which protein folding occurs incorrectly, such as in the so-called protein folding disorders, which include Alzheimer's, Parkinson's, tumoral, and prion diseases. Because partially folded intermediates, leading in some cases to misfolding and the occurrence of protein aggregates, are stabilized by pressure, the application of high pressure permits the characterization of these aggregation reactions.

Rangel L.P.,Institute Bioquimica Medica Leopoldo Of Meis | Rangel L.P.,Brazilian National Institute of Technology | Rangel L.P.,Federal University of Rio de Janeiro | Costa D.C.F.,Institute Bioquimica Medica Leopoldo Of Meis | And 5 more authors.
Prion | Year: 2014

The tumor suppressor protein p53 loses its function in more than 50% of human malignant tumors. Recent studies have suggested that mutant p53 can form aggregates that are related to loss-of-function effects, negative dominance and gain-of-function effects and cancers with a worsened prognosis. In recent years, several degenerative diseases have been shown to have prion-like properties similar to mammalian prion proteins (PrPs). However, whereas prion diseases are rare, the incidence of these neurodegenerative pathologies is high. Malignant tumors involving mutated forms of the tumor suppressor p53 protein seem to have similar substrata. The aggregation of the entire p53 protein and three functional domains of p53 into amyloid oligomers and fibrils has been demonstrated. Amyloid aggregates of mutant p53 have been detected in breast cancer and malignant skin tumors. Most p53 mutations related to cancer development are found in the DNA-binding domain (p53C), which has been experimentally shown to form amyloid oligomers and fibrils. Several computation programs have corroborated the predicted propensity of p53C to form aggregates, and some of these programs suggest that p53C is more likely to form aggregates than the globular domain of PrP. Overall, studies imply that mutant p53 exerts a dominant-negative regulatory effect on wild-type (WT) p53 and exerts gain-of-function effects when co-aggregating with other proteins such as p63, p73 and acetyltransferase p300. We review here the prion-like behavior of oncogenic p53 mutants that provides an explanation for their dominant-negative and gain-of-function properties and for the high metastatic potential of cancers bearing p53 mutations. The inhibition of the aggregation of p53 into oligomeric and fibrillar amyloids appears to be a promising target for therapeutic intervention in malignant tumor diseases.©2014 Landes Bioscience.

Grativol C.,Institute Bioquimica Medica Leopoldo Of Meis | Regulski M.,Cold Spring Harbor Laboratory | Bertalan M.,MHS Capital | McCombie W.R.,Cold Spring Harbor Laboratory | And 8 more authors.
Plant Journal | Year: 2014

Many economically important crops have large and complex genomes that hamper their sequencing by standard methods such as whole genome shotgun (WGS). Large tracts of methylated repeats occur in plant genomes that are interspersed by hypomethylated gene-rich regions. Gene-enrichment strategies based on methylation profiles offer an alternative to sequencing repetitive genomes. Here, we have applied methyl filtration with McrBC endonuclease digestion to enrich for euchromatic regions in the sugarcane genome. To verify the efficiency of methylation filtration and the assembly quality of sequences submitted to gene-enrichment strategy, we have compared assemblies using methyl-filtered (MF) and unfiltered (UF) libraries. The use of methy filtration allowed a better assembly by filtering out 35% of the sugarcane genome and by producing 1.5× more scaffolds and 1.7× more assembled Mb in length compared with unfiltered dataset. The coverage of sorghum coding sequences (CDS) by MF scaffolds was at least 36% higher than by the use of UF scaffolds. Using MF technology, we increased by 134× the coverage of gene regions of the monoploid sugarcane genome. The MF reads assembled into scaffolds that covered all genes of the sugarcane bacterial artificial chromosomes (BACs), 97.2% of sugarcane expressed sequence tags (ESTs), 92.7% of sugarcane RNA-seq reads and 98.4% of sorghum protein sequences. Analysis of MF scaffolds from encoded enzymes of the sucrose/starch pathway discovered 291 single-nucleotide polymorphisms (SNPs) in the wild sugarcane species, S. spontaneum and S. officinarum. A large number of microRNA genes was also identified in the MF scaffolds. The information achieved by the MF dataset provides a valuable tool for genomic research in the genus Saccharum and for improvement of sugarcane as a biofuel crop. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Almeida R.M.V.R.,Federal University of Rio de Janeiro | de Albuquerque Rocha K.,Institute Bioquimica Medica Leopoldo Of Meis | Catelani F.,Federal University of Rio de Janeiro | Fontes-Pereira A.J.,Federal University of Rio de Janeiro | Vasconcelos S.M.R.,Institute Bioquimica Medica Leopoldo Of Meis
Science and Engineering Ethics | Year: 2015

This study focuses on retraction notices from two major Latin American/Caribbean indexing databases: SciELO and LILACS. SciELO includes open scientific journals published mostly in Latin America/the Caribbean, from which 10 % are also indexed by Thomson Reuters Web of Knowledge Journal of Citation Reports (JCR). LILACS has a similar geographical coverage and includes dissertations and conference/symposia proceedings, but it is limited to publications in the health sciences. A search for retraction notices was performed in these two databases using the keywords “retracted”, “retraction” “withdrawal”, “withdrawn”, “removed” and “redress”. Documents were manually checked to identify those that actually referred to retractions, which were then analyzed and categorized according to the reasons alleged in the notices. Dates of publication/retraction and time to retraction were also recorded. Searching procedures were performed between June and December 2014. Thirty-one retraction notices were identified, fifteen of which were in JCR-indexed journals. “Plagiarism” was alleged in six retractions of this group. Among the non-JCR journals, retraction reasons were alleged in fourteen cases, twelve of which were attributed to “plagiarism”. The proportion of retracted articles for the SciELO database was approximately 0.005 %. The reasons alleged in retraction notices may be used as signposts to inform discussions in Latin America on plagiarism and research integrity. At the international level, these results suggest that the correction of the literature is becoming global and is not limited to mainstream international publications. © 2015 Springer Science+Business Media Dordrecht

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