The N-terminus of the human dihydroorotate dehydrogenase (HsDHODH) has been described as important for the enzyme attachment in the inner mitochondrial membrane and possibly to regulate enzymatic activity. In this study, we synthesized the peptide acetyl-GDERFYAEHLMPTLQGLLDPESAHRL AVRFTSLGamide, comprising the residues 33-66 of HsDHODH N-terminal conserved microdomain. Langmuir monolayers and circular dichroism (CD) were employed to investigate the interactions between the peptide and membrane model, as micelles and monolayers of the lipids phosphatidylcholine (PC), 3-phosphatidylethanolamine (PE) and cardiolipin (CL). These lipids represent the major constituents of inner mitochondrial membranes. According to CD data, the peptide adopted a random structure in water, whereas it acquired α-helical structures in the presence of micelles. The π-A isotherms and polarization- modulated infrared reflection-absorption spectroscopy on monolayers showed that the peptide interacted with all lipids, but in different ways. In DPPC monolayers, the peptide penetrated into the hydrophobic region. The strongest initial interaction occurred with DPPE, but the peptide was expelled from this monolayer at high surface pressures. In CL, the peptide could induce a partial dissolution of the monolayer, leading to shorter areas at the monolayer collapse. These results corroborate the literature, where the HsDHODH microdomain is anchored into the inner mitochondrial membrane. Moreover, the existence of distinct conformations and interactions with the different membrane lipids indicates that the access to the enzyme active site may be controlled not only by conformational changes occurring at the microdomain of the protein, but also by some lipid-protein synergetic mechanism, where the HsDHODH peptide would be able to recognize lipid domains in the membrane.

The usefulness of coordination metal compounds in cancer chemotherapy was firstly demonstrated by Cisplatin. As a result of an intense research on the field of copper complexes with antitumor activity, copper coordination compounds are emerging as an alternative for the development of drugs for the treatment cancer. Our research is devoted to find new metal containing drugs for the treatment of cancer. This paper summarizes our results on the study of Copper-diimine of ternary complexes and related Copper homoleptic complexes as cytotoxic agents. The studied diimines were 2,2-dipyridil-amine, bypiridine, 4,4´-2,2´bipyridine, 1,10 phenanthroline, 4-methyl-1,10 phenanthroline, 5-NO 2 -phenanthroline, neocuproine and bathophenanthroline. L-dipeptides, iminodiacetic acid or phosphines were used as coligands. Most of the complexes present higer cytotoxicity than Cisplatin. We hypothesize that the cation [Cu(diimine) ] 2+ is the active species of the complexes.

This Commentary describes a call for submissions for the upcoming Special Issue focused on the science presented at the 20 th IUPAB Congress to be held in conjunction with the 45 th Annual Meeting of the Brazilian Biophysical Society and the 49 th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology.

Resumo Esse estudo faz uma análise estatística multivariada de componentes principais (ACP) para estabelecer padrões de desempenho escolar para o 5° e o 9° ano do Ensino Fundamental das escolas municipais de Ribeirão Preto. As equações matemáticas obtidas de gráficos bidimensionais de ACP revelam que os percentuais de alunos com aprendizado adequado em língua portuguesa e em matemática são os indicadores mais significativos para explicar tais padrões de desempenho. A partir dessa análise, foi possível estabelecer vetores de desempenho escolar para cada uma das escolas dos dois anos escolares do Ensino Fundamental aqui considerados. Isso permitiu construir um indicador de heterogeneidade para as escolas da rede municipal de Educação de Ribeirão Preto.

Corticosteroid-binding globulin (CBG) is a blood plasma protein that transports the weakly water-soluble hormone, cortisol, throughout the circulation. It is a member of the serine protease inhibitor (SERPIN) structural family; upon cleavage by human neutrophil elastase, it undergoes the canonical S-to-R transition, which results in a change in its binding affinity for cortisol, allowing it to release the hormone at sites of inflammation. We plan to redesign CBG to transport compounds other than its physiological ligand and, by harnessing the S-to-R transition, release them at specific sites in the body. In preliminary experiments, we succeeded in altering the proteinase specificity of CBG, making it susceptible to cleavage by human αthrombin. We plan to build on this and prove the principle that by altering the amino acid sequence of the reactive centre loop, CBG can be made to release its ligand in response to specific cleavage by various proteinases. We are especially interested in making it susceptible to proteinases that are tissue-specific so that the engineered protein would be able to deliver its cargo at very specific sites in the body. We are also looking at redesigning the steroid-binding pocket of CBG so that it is able to bind other compounds with high affinities. Apart from that, it is also necessary to make the change in affinity between the S-state and the R-state much larger should the engineered protein ever be considered for use as a drug-delivery system. In order to study the binding site, and to understand in depth how the change in binding affinity is achieved by the S-to-R transition, it is necessary to obtain crystal structures of CBG in both forms from the same organism as the structures currently available for the native and cleaved forms of CBG are from different organisms [1], [2]. This makes it difficult to tell if the differences in the positions of various residues in the binding pocket are due to conformational changes or a lack of sequence identity. These structural studies will be complemented with molecular modeling and biochemical experiments to determine how the residues lining the binding pocket contribute to ligand binding and to the mechanism that results in the change in ligand-binding affinity following proteolytic cleavage of the reactive centre loop. Whilst studying other factors that can affect ligand binding, we also discovered that binding affinity decreases when temperature increases, even within the small range allowed physiologically. This observation was corroborated by a recent study by Cameron et al [3]. We think this is another property we can exploit because the local temperature in different parts of the body can vary with tissue type and disease state, and consequently may add another level of specificity for the release of potentially therapeutic compounds from the engineered protein.