Analytical applications of partitioning in aqueous two-phase systems: Exploring protein structural changes and protein–partner interactions in vitro and in vivo by solvent interaction analysis method

Zaslavsky, Boris Y.; Uversky, Vladimir N.; Chait, Arnon

doi:10.1016/j.bbapap.2016.02.017

Cited by 39 publications

(33 citation statements)

References 248 publications

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“…Considered together, these observations and considerations support an important notion: the analysis of the protein expression levels in biological fluids may not be the optimal focus of clinical proteomic research and that novel proteomic approaches are needed for the discovery of structure- and function-based next generation or smart biomarkers [151,152]. …”

Section: Discussionmentioning

confidence: 99%

Cancer/Testis Antigens: “Smart” Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers

Kulkarni

Uversky

2017

IJMS

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A clinical dilemma in the management of prostate cancer (PCa) is to distinguish men with aggressive disease who need definitive treatment from men who may not require immediate intervention. Accurate prediction of disease behavior is critical because radical treatment is associated with high morbidity. Here, we highlight the cancer/testis antigens (CTAs) as potential PCa biomarkers. The CTAs are a group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. Interestingly, >90% of CTAs are predicted to belong to the realm of intrinsically disordered proteins (IDPs), which do not have unique structures and exist as highly dynamic conformational ensembles, but are known to play important roles in several biological processes. Using prostate-associated gene 4 (PAGE4) as an example of a disordered CTA, we highlight how IDP conformational dynamics may regulate phenotypic heterogeneity in PCa cells, and how it may be exploited both as a potential biomarker as well as a promising therapeutic target in PCa. We also discuss how in addition to intrinsic disorder and post-translational modifications, structural and functional variability induced in the CTAs by alternate splicing represents an important feature that might have different roles in different cancers. Although it is clear that significant additional work needs to be done in the outlined direction, this novel concept emphasizing (multi)functionality as an important trait in selecting a biomarker underscoring the theranostic potential of CTAs that is latent in their structure (or, more appropriately, the lack thereof), and casts them as next generation or “smart” biomarker candidates.

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Section: Discussionmentioning

confidence: 99%

Cancer/Testis Antigens: “Smart” Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers

Kulkarni

Uversky

2017

IJMS

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“…The components of each phase are immiscible despite containing about 80% water (molal base). Each phase has different characteristics, which allows them to partition a sample with different molecules (Zaslavsky et al, 2016). They are considered as a primary recovery stage for the separation of biological molecules, due to the large amount of water they contain.…”

Section: Laccase As By-product From Food Industrymentioning

confidence: 99%

Laccases in Food Industry: Bioprocessing, Potential Industrial and Biotechnological Applications

Mayolo‐Deloisa

González‐González

Rito‐Palomares

2020

Front. Bioeng. Biotechnol.

121

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Laccase is a multi-copper oxidase that catalyzes the oxidation of one electron of a wide range of phenolic compounds. The enzyme is considered eco-friendly because it requires molecular oxygen as co-substrate for the catalysis and it yields water as the sole by-product. Laccase is commonly produced by fungi but also by some bacteria, insects and plants. Due it is capable of using a wide variety of phenolic and nonphenolic substrates, laccase has potential applications in the food, pharmaceutical and environmental industries; in addition, it has been used since many years in the bleaching of paper pulp. Fungal laccases are mainly extracellular enzyme that can be recovered from the residual compost of industrial production of edible mushrooms as Agaricus bisporus and Pleurotus ostreatus. It has also been isolated from microorganisms present in wastewater. The great potential of laccase lies in its ability to oxidize lignin, one component of lignocellulosic materials, this feature can be widely exploited on the pretreatment for agro-food wastes valorization. Laccase is one of the enzymes that fits very well in the circular economy concept, this concept has more benefits over linear economy; based on "reduce-reuse-recycle" theory. Currently, biorefinery processes are booming due to the need to generate clean biofuels that do not come from oil. In that sense, laccase is capable of degrading lignocellulosic materials that serve as raw material in these processes, so the enzyme's potential is evident. This review will critically describe the production sources of laccase as by-product from food industry, bioprocessing of food industry by-products using laccase, and its application in food industry.

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“…In general, the effect of the polymer MW in the protein partition is commonly associated with at least one of the two following phenomena: (i) steric exclusion of the protein; 45,46 (ii) increase of the relative hydrophobicity of the polymer rich-phase (reduction of hydrophilic groups/hydrophobic area ratio). 19,27,47,48 The excluded volume effect implies that interactions between polymer and protein are limited to the absence of steric overlap, where small polymer molecules can occupy the entire volume fraction not filled with protein, 49 while the increase of relative hydrophobicity of the polymer-rich phase favors the partition of hydrophobic proteins into it (due to the hydrophobic interaction between the non-polar amino acid residues of the proteins and the ethylene groups of the PEG). 50 However, note that the most hydrophobic PEG can be excluded from hydrophilic domains of the proteins, decreasing its solubility in the PEG-rich phase.…”

Section: Control Of Asnase Partition By Selecting the Nature Of Polymmentioning

confidence: 99%

Controlling the l‐asparaginase extraction and purification by the appropriate selection of polymer/salt‐based aqueous biphasic systems

Magri

Pimenta

Santos

et al. 2019

J of Chemical Tech & Biotech

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BACKGROUND l‐Asparaginase (ASNase) is an important biopharmaceutical for the treatment of acute lymphoblastic leukemia (ALL); however, with some restrictions due to its high manufacturing costs. Aqueous biphasic systems (ABS) have been suggested as more economical platforms for the separation/purification of proteins, but a full understanding of the mechanisms behind the ASNase partition is still a major challenge. Polymer/salt‐based ABS with different driving‐forces (salting‐out and hydrophilicity/hydrophobicity effects) were herein applied to control the partition of commercial ASNase. RESULTS The main results showed the ASNase partition to the salt‐ or polymer‐rich phase depending on the ABS studied, with extraction efficiencies higher than 95%. For systems composed of inorganic salts, the ASNase partition was controlled by the polyethylene glycol (PEG) molecular weight used. Cholinium‐salts‐based ABS were able to promote a preferential ASNase partition to the polymer‐rich phase using PEG‐600 and to the salt‐rich phase using a more hydrophobic polypropylene glycol (PPG)‐400 polymer. It was possible to select the ABS composed of PEG‐2000 + potassium phosphate buffer as the most efficient to separate the ASNase from the main contaminant proteins (purification factor = 2.4 ± 0.2), while it was able to maintain the enzyme activity for posterior application as part of a therapeutic. CONCLUSION Polymer/salt ABS can be used to control the partition of ASNase and adjust its purification yields, demonstrating the ABS potential as more economic platform for the selective recovery of therapeutic enzymes from complex broths. © 2019 Society of Chemical Industry

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Analytical applications of partitioning in aqueous two-phase systems: Exploring protein structural changes and protein–partner interactions in vitro and in vivo by solvent interaction analysis method

Cited by 39 publications

References 248 publications

Cancer/Testis Antigens: “Smart” Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers

Cancer/Testis Antigens: “Smart” Biomarkers for Diagnosis and Prognosis of Prostate and Other Cancers

Laccases in Food Industry: Bioprocessing, Potential Industrial and Biotechnological Applications

Controlling the l‐asparaginase extraction and purification by the appropriate selection of polymer/salt‐based aqueous biphasic systems

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