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Current Protein & Peptide Science

Lisbell D Estrada, Luciana Oliveira-Cruz, Daniel Cabrera
Alzheimer's disease is a neurodegenerative condition affecting millions of people worldwide. Alzheimer's symptoms include memory loss and cognitive decline. Pathologically, the hallmarks of Alzheimer´s are the presence of Amyloid beta-plaques, neurofibrillary tangles, and neuronal loss. Unfortunately, no cure is presently available and current treatments are only symptomatic. Transforming growth factor beta type I (TGF-β1) is a trophic factor involved in neuronal development and synaptic plasticity...
November 28, 2017: Current Protein & Peptide Science
Sebastian Gatica, Claudio Cabello-Verrugio, Felipe Simon
This review includes a comprehensive, but succinct, summary on the essentials of TGF-b structure, family members, receptors, and intracellular mediators. Also provided is a select list of original publications that report novel roles and facets of TGF-b in vascular function and signaling in the contexts of health and disease.
November 27, 2017: Current Protein & Peptide Science
Marco Arrese, Daniel Cabrera, Alejandra Hernandez, Luis Astete, Lisbell Estrada, Claudio Cabello-Verrugio
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide accounting for more than 700 thousand deaths per year. Most of the HCC develops in a cirrhotic liver, a microenvironment where fibrotic tissue replaces parenchymal cells. Thus, there is a close connection between fibrosis and HCC development. Understanding the cellular and molecular mechanisms involved in this process is a crucial step to advance in novel therapeutic or pharmacological strategies to prevent or improve the course of this malignancy...
November 16, 2017: Current Protein & Peptide Science
Tsutomu Arakawa, Masao Tokunaga, Takuya Maruyama, Kentarou Shiraki
MEP (mercapto-ethyl-pyridine) HyperCel is one of the hydrophobic charge induction chromatography (HCIC) resins. Under normal operation, proteins are bound to the MEP resin at neutral pH, at which MEP is not charged, mostly via hydrophobic interaction. MEP has a pyridine group, whose pK is 4.8, and hence is positively charged at acidic pH range. Based on the binding mechanism (i.e., hydrophobic interaction) and the induced positive charge at acidic pH, there may be two ways to elute the bound proteins. One way is to bring the pH down to protonate both MEP resin and the bound protein, leading to charge repulsion and thereby elution...
November 16, 2017: Current Protein & Peptide Science
Larisa Ryskalin, Carla L Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella, Francesco Fornai
Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owing an abnormal structure (as occurring following point gene mutations)...
November 16, 2017: Current Protein & Peptide Science
Johanna Abrigo, Felipe Simon, Daniel Cabrera, Gonzalo Cordova, Capucine Trollet, Claudio Cabello Verrugio
Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-b1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-b has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-b1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy...
November 16, 2017: Current Protein & Peptide Science
Jelena Krstic, Drenka Trivanovic, Hristina Obradovic, Tamara Kukolj, Diana Bugarski, Juan F Santibanez
The ability to differentiate into cells of different lineage, such as muscle, bone, cartilage and fat, is the chief value of adult mesenchymal stem cells (MSCs) which can be used with the final aim to regenerate damaged tissue. Due to potential use, as well as importance in tissue development, a number of questions have been raised regarding the molecular mechanisms of MSC differentiation. As one of the crucial mediators in organism development, transforming growth factor beta (TGF-β) superfamily directs MSCs commitment in the selection of differentiation pathways...
November 16, 2017: Current Protein & Peptide Science
Charlotte Cabanne, Xavier Santarelli
Mixed mode chromatography resins with salt tolerance, large design space and orthogonal selectivity requires a slightly more complex development than traditional resins. It is important to screen several ligands and several binding and elution conditions. This allows taking full advantage of these resins. High-Throughput Screening (HTS) for Process Development should be done with the help of Design of Experiment (DoE). It could be performed in filter plates or Robocolumns, and assisted by liquid handling automated workstation...
October 29, 2017: Current Protein & Peptide Science
Andrea Bellelli
Hemoglobin (Hb) is the prototypical example of a cooperative protein. Cooperativity of Hb is largely accounted for by an allosteric structural change between the T and R quaternary structures. Allostery is such a powerful explanation of Hb cooperativity that the possibility of cooperative events occurring within each allosteric conformation, in the absence of any quaternary structural change has usually been overlooked, and actually experiments specifically aimed at detecting non-allosteric cooperativity have usually failed to do so...
October 29, 2017: Current Protein & Peptide Science
Juan F Santibanez, Jelena Krstic
Transforming growth factor beta (TGF-β) is well recognized as playing a double role in tumor progression. Its antitumor role takes place in the early stages of caner development, when TGF-β acts as a repressor of epithelial tumor growth. In advanced stages of cancer development, TGF-β has a tumor stimulating role, acting concomitantly with the increase of cancer cell migration and metastasis. One of the critical features of cancer cells is their ability to migrate and invade the surrounding tissues leading to metastases in different organs...
October 29, 2017: Current Protein & Peptide Science
Elizabeth A Kulikova, Alexander V Kulikov
Kaiso is a bimodal transcriptional repressor. It binds methylated CpG islands or the sequence-specific consensus in the DNA molecule with the Kaiso zinc-finger domain and recruits repressive protein complexes to these DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR1 corepressor and histone deacetylase, thereby performing transcription repression. Kaiso is involved in epigenetic regulation of transcription. Moreover, the complex Kaiso and catenin p120ctn modulates the transcription of the Wnt-target genes...
October 29, 2017: Current Protein & Peptide Science
Tsutomu Arakawa, Yoshiko Kita
Previously, we have reviewed in this journal (Arakawa, T., Kita, Y., Curr. Protein Pept. Sci., 15, 608-620, 2014) the interaction of arginine with proteins and various applications of this solvent additive in the area of protein formulations and downstream processes. In this special issue, we expand the concept of protein-solvent interaction into the analysis of the effects of solvent additives on various column chromatography, including mixed-mode chromatography. Earlier in our research, we have studied the interactions of such a variety of solvent additives as sugars, salts, amino acids, polymers and organic solvents with a variety of proteins, which resulted in mechanistic understanding on their protein stabilization and precipitation effects, the latter known as Hofmeister series...
October 24, 2017: Current Protein & Peptide Science
Daisuke Itoh, Noriko Yoshimoto, Shuichi Yamamoto
Retention mechanism of proteins in hydroxyapatite chromatography (HAC) was investigated by linear gradient elution experiments. Several mobile phase (buffer) solution strategies and solutes were evaluated in order to probe the relative contributions of two adsorption sites of hydroxyapatite (HA) particles, C-site due to Ca (metal affinity) and P-site due to PO4 (cation-exchange). When P-site was blocked, two basic proteins, lysozyme (Lys) and ribonuclease A(RNase), were not retained whereas cytochrome C(Cyt C) and lactoferrin (LF) were retained and also retention of acidic proteins became stronger as the repulsion due to P-site was eliminated...
October 24, 2017: Current Protein & Peptide Science
Tiago Matos, Leif Bulow
The needs for purified nucleic acids for preparative and analytical applications have increased constantly, demanding for the development of new and more efficient methods for their recovery and isolation. DNA molecules harbour some intrinsic chemical properties that render them suitable for chromatographic separations. These include a negatively charged phosphate backbone as well as a hydrophobic character originating mainly from the major groove of DNA which exposes the base pairs on the surface of the molecule...
October 24, 2017: Current Protein & Peptide Science
Xavier Santarelli, Charlotte Cabanne
Mixed mode chromatography offers a diversity of ligands, each providing a new selectivity. This allows the design of novel purification processes with reduced column steps. Structure of ligands is based on both hydrophobic and ionic groups. Thanks to its salt tolerance, crude extracts or post-IEX samples can be loaded directly without conditioning. The selectivity could be enhanced by modulating elution parameters or by using additives. More importantly, mixed mode chromatography could be as effective as affinity chromatography for mAb purification processes...
October 24, 2017: Current Protein & Peptide Science
Atsushi Hirano, Kentarou Shiraki, Tomoshi Kameda
Multimodal or mixed-mode chromatography can be used to separate various proteins, including antibodies. The separation quality and efficiency have been improved by the addition of solutes, especially arginine. This review summarizes the mechanism underlying the effects of arginine on protein elution in multimodal chromatography with neutral, anionic or cationic resin ligands; the mechanism has been investigated using experiments and molecular dynamics simulations. Arginine is effective in facilitating protein elution compared to salts and protein denaturants such as guanidine and urea...
October 24, 2017: Current Protein & Peptide Science
Vivek Halan, Sunit Maity, Rahul Bhambure, Anurag S Rathore
Process chromatography forms the core of purification of biotherapeutics. The unparalleled selectivity that it offers over other alternatives combined with the considerable robustness and scalability make it the unit operation of choice in downstream processing. It is typical to have three to five chromatography steps in a purification process for a biotherapeutic. Generally, these steps offer different modes of separation such as ion-exchange, reversed phase, size exclusion, and hydrophobic interaction. In the past decade, multimodal chromatography has emerged as an alternative to the traditional modes...
October 20, 2017: Current Protein & Peptide Science
Xuemei M He, Carsten VoB, Jidong Li
Mixed-mode chromatography is becoming an important tool for downstream process purification, as it provides the selectivity and robustness unmatched by conventional single-mode chromatographic methods. The joint action of multiple functionalities present on the ligands of mixed-mode chromatography matrices effectively enhances the separation of target molecules from impurities. Using Nuvia cPrime as an example, we elucidate the separation principles of hydrophobic cation exchange mixed-mode chromatography and its difference from traditional strong cation exchangers...
October 17, 2017: Current Protein & Peptide Science
Xiaoju Tang, Ling Sun, Gang Wang, Bojiang Chen, Fengming Luo
Runt-related transcription factor 1 (RUNX1), a member of the RUNX family, is one of the key regulatory proteins in vertebrates. RUNX1 is involved in embryonic development, hematopoiesis, angiogenesis, tumorigenesis and immune response. In the past few decades, studies mainly focused on the effect of RUNX1 on acute leukemia and cancer. Only few studies about the function of RUNX1 in the pathological process of pulmonary diseases have been reported. Recent studies have demonstrated that RUNX1 is highly expressed in both mesenchymal and epithelial compartments of the developing and postnatal lung and that it plays a critical role in the lipopolysaccharide induced lung inflammation by regulating the NF-κB pathway...
October 9, 2017: Current Protein & Peptide Science
Tsutomu Arakawa
TOYOPEARL particles are cross-linked hydroxylated methacrylic polymers available in different pore and particle sizes. They are conjugated with different ligands to generate ion-exchange, hydrophobic interaction and affinity resins. They have excellent physical and chemical properties. A mixed-mode resin, TOYOPEARL MX-Trp-650M, is made of this particle with tryptophan conjugated via N-terminal amino group and hence has both hydrophobic/aromatic side chain and carboxyl group. In this review, I will summarize the properties of the TOYOPEARL particles and MX-Trp-650M resin and application of this resin for purification of proteins and in some detail the separation of disulfide (SS)-scrambled oligomers of insulin-like growth factor-1 (IGF-1)...
October 9, 2017: Current Protein & Peptide Science
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