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Y., Eva; Krishnan, Sampathkumar; Randolph, Theodore W.; Carpenter, John F.

doi:10.1023/a:1025771421906

Cited by 1,229 publications

(475 citation statements)

References 82 publications

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“…Proteins often show this behaviour in solution with cations present. 49,50,57 Also, the electrostatic interactions cause structural alterations in the proteins' secondary structure as the CD spectra of Mb, Cyt c and Ub indicate severe spectral changes in solution upon addition of the metallaprisms.…”

Section: Organic and Biomolecular Chemistry Papermentioning

confidence: 99%

Interactions of arene ruthenium metallaprisms with human proteins

2015

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Interactions between three hexacationic arene ruthenium metallaprisms, [( p-cymene) 6+ , and a series of human proteins including human serum albumin, transferrin, cytochrome c, myoglobin and ubiquitin have been studied using NMR spectroscopy, mass spectrometry and circular dichroism spectroscopy. All data suggest that no covalent adducts are formed between the proteins and the metallaprisms. Indeed, in most cases electrostatic interactions, leading to precipitation of protein-metallaprism aggregates, have been observed. In addition, with the smallest proteins, ubiquitin, myoglobin and cytochrome c, the presence of the hexacationic arene ruthenium metallaprisms induces structural changes of the proteins, as emphasized by circular dichroism. The results suggest that proteins are certainly a biological target for these metalla-assemblies.

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Section: Organic and Biomolecular Chemistry Papermentioning

confidence: 99%

Interactions of arene ruthenium metallaprisms with human proteins

2015

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“…At pH values close to the isoelectric point, protein−protein interactions can be highly attractive, leading to protein aggregation, by self-association. 8 The solution stability of a protein is also influenced by the salt concentration. The salt ions interact strongly with the water molecules surrounding the protein, thereby screening the long-range electrostatic repulsion and enhancing attractive van der Waals and hydrophobic effects.…”

Section: −28mentioning

confidence: 99%

Thermal and Solution Stability of Lysozyme in the Presence of Sucrose, Glucose, and Trehalose

James

McManus

2012

J. Phys. Chem. B

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The effect of the sugars sucrose, glucose, and trehalose on the structural and colloidal stability of lysozyme has been investigated using differential scanning calorimetry and quasi-elastic light scattering, respectively. While sugars are known to increase the temperature at which thermal denaturation of protein occurs, it is not clear if, under the same solution conditions, greater colloidal stability is achieved. The measurements were carried out on lysozyme in three different buffer solutions, 0.05 M sodium acetate (pH 4.6), 0.05 M sodium acetate with 5% (w/v) NaCl, and 10 mM sodium phosphate (pH 7.0). The results show that enhancement of structural stability in the presence of sugars is pH, salt concentration, and sugar dependent. Enhancement of colloidal stability in the presence of sugars, while also pH and salt concentration dependent, as expected, only correlates with increases in the structural stability when the solution behavior is not dominated by highly stabilizing electrostatic repulsive interactions. ■ INTRODUCTIONSugars are widely used excipients in the formulation of biotherapeutic products.1−7 Therapeutic proteins are produced and used for the treatment of various human diseases 8 such as insulin for the treatment of diabetes, 9 monoclonal antibodies for rheumatoid arthritis, 10 interferon-α for leukemia, 11 and interferon-β for multiple sclerosis.12 Sugars are generally used as protein structure stabilizers, 2,13 since additional stability is conferred to a protein during lyophilization by the addition of the sugar.14 Two hypotheses have been proposed to describe the stabilizing effect of sugars on proteins during lyophilization; one such hypothesis states that sugar acts as a water substituent and stabilizes proteins by forming hydrogen bonds at specific sites on the surface of the protein.14−16 Another hypothesis, referred to as the "vitrification hypothesis", states that disaccharides form sugar glasses, thereby immobilizing the protein molecules and providing protection against destabilizing reactions. 15,16 Lysozyme is a globular protein with a molecular weight of approximately 14.7 kDa. Lysozyme has been used as a model protein for this study, since its biophysical properties are well understood and the specific contribution of the sugar to its stability over a range of solution conditions can easily be compared with that of the native protein. Lysozyme is a widely studied protein due to its rich phase behavior 17,18 including crystallization, 19 liquid−liquid phase separation, 20−22 and the formation of equilibrium clusters 23−25 and gels. 24 The solution behavior of lysozyme is also well understood in terms of its interaction with salt ions. 26−28Protein stability by itself is a generic term, and it can be thought of in several ways. The stabilization of protein structure against thermal denaturation is referred to as its thermal or structural stability. 37 and presence of excipients. 6 At pH values away from the isoelectric point of the protein, there is an increase in cha...

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“…Assim, mudanças no pH vão afetar a distribuição de cargas de uma proteína e, conseqüentemente, as interações eletrostáticas entre grupos da proteína, entre a proteína e o solvente e entre as próprias moléculas do solvente 20,[24][25][26] . A mudança do pH do meio de um valor i para um valor j vai promover alterações na energia livre tanto do estado N quanto do…”

Section: Equilíbrio De Estabilização De Proteínas Como Uma Função Do Phunclassified

Efeito da composição do solvente sobre a estabilidade de proteínas em soluções aquosas

Fonseca

Corrêa²,

Garrote-Filho³

et al. 2006

Quím. Nova

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Recebido em 14/3/05; aceito em 21/7/05; publicado na web em 8/2/06 EFFECTS OF THE SOLVENT COMPOSITION ON THE STABILITY OF PROTEINS IN AQUEOUS SOLUTIONS. A protein presents a native (N) macro state, which is functionally active, in equilibrium with the denatured (D) macro state, which is devoid of biological activity. An ensemble of microstates forms each macrostate. The denatured state comprises a greater ensemble of microstates than the native macrostate. The N-D equilibrium can be affected by several factors, that comprise the purity of the water, temperature, pH and solute concentration. This work discusses the influence of osmolytes and chaotropics on the N-D equilibrium in aqueous solutions.Keywords: chaotropics; protein stability; osmolytes. INTRODUÇÃOAs proteínas são fundamentais para os seres vivos e podem desempenhar diversas funções, desde a organização estrutural de uma célula até as organizações anatômicas de um organismo vivo, além de atuarem como enzimas, que catalisam as mais diversas reações metabólicas indispensáveis à vida.Uma proteína pode estar no estado nativo (N), em que apresenta a função para a qual foi produzida, ou no estado desnaturado (D), em que não apresenta uma função específica, embora ainda seja uma fonte de aminoácidos, que podem ser usados no catabolismo energético e em vários processos de biossíntese.Uma proteína pode apresentar inúmeras conformações. Cada uma delas caracteriza um micro-estado. O conjunto ("ensemble") desses micro-estados compõe o macro-estado da proteína. O macroestado N é composto por uma quantidade pequena de micro-estados, uma vez que a estrutura da proteína não deve variar muito, para não comprometer sua função. Mas o macro-estado D pode apresentar um número muito elevado de micro-estados 1,2 . Os estados N e D de uma proteína estão em equilíbrio N Donde predomina o estado que apresenta menor conteúdo de energia livre e, portanto, maior estabilidade 1-4 . Em soluções essencialmente aquosas, o estado N tem maior estabilidade, o que é fundamental para preservar a função da proteína. Vários fatores, como temperatura, pH e concentração de solutos, podem afetar o equilíbrio N-D, promovendo estabilização (do estado nativo) ou desnaturação. A estabilização e a desnaturação de proteínas são temas de grande interesse fisiológico 5 , terapêutico 6,7 e biotecnológico 8,9 , onde o controle da estabilidade de uma proteína representa uma importante estratégia para manutenção de sua atividade biológica. Além disso, atualmente a análise da estabilidade se tornou um instrumento poderoso para caracterização de proteínas [10][11][12] , cada vez mais utilizado na literatura com este propósito [13][14][15][16] . A estabilização e desnaturação de proteínas têm sido revistas em trabalhos clássi-cos, que mostram a natureza complexa desses processos [17][18][19][20][21][22] . O presente trabalho procura se inserir neste contexto, fazendo uma revisão analítica sobre a natureza termodinâmica do efeito da água pura, de caotrópicos e osmólitos sobre a estabilidade de proteínas em sol...

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Untitled

Cited by 1,229 publications

References 82 publications

Interactions of arene ruthenium metallaprisms with human proteins

Interactions of arene ruthenium metallaprisms with human proteins

Thermal and Solution Stability of Lysozyme in the Presence of Sucrose, Glucose, and Trehalose

Efeito da composição do solvente sobre a estabilidade de proteínas em soluções aquosas

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