ResearchPad - solubility https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Insight into the protein solubility driving forces with neural attention]]> https://www.researchpad.co/article/elastic_article_13832 The solubility of proteins is a crucial biophysical aspect when it comes to understanding many human diseases and to improve the industrial processes for protein production. Due to its relevance, computational methods have been devised in order to study and possibly optimize the solubility of proteins. In this work we apply a deep-learning technique, called neural attention to predict protein solubility while “opening” the model itself to interpretability, even though Machine Learning models are usually considered black boxes. Thank to the attention mechanism, we show that i) our model implicitly learns complex patterns related to emergent, protein folding-related, aspects such as to recognize β-amyloidosis regions and that ii) the N-and C-termini are the regions with the highes signal fro solubility prediction. When it comes to enhancing the solubility of proteins, we, for the first time, propose to investigate the synergistic effects of tandem mutations instead of “single” mutations, suggesting that this could minimize the number of required proposed mutations.

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<![CDATA[Cyclodextrins as multifunctional excipients: Influence of inclusion into β-cyclodextrin on physicochemical and biological properties of tebipenem pivoxil]]> https://www.researchpad.co/article/5c57e6e3d5eed0c484ef418c

A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed. The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system. The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach. The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state. Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco–2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity. The proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.

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<![CDATA[Physicochemical characteristics and high sensory acceptability in cappuccinos made with jackfruit seeds replacing cocoa powder]]> https://www.researchpad.co/article/5b8acde340307c144d0de054

Jackfruit seeds are an under-utilized waste product in many tropical countries. In this work, we demonstrate the potential of roasted jackfruit seeds to substitute for cocoa powder in cappuccino formulations. Two different flours were produced from a hard variety jackfruit by drying or fermenting the seeds prior to roasting. Next, formulations were prepared with 50%, 75%, and 100% substitution of cocoa powder with jackfruit seed flours, totalizing seven with control formulation. The acceptance of cappuccinos by consumers (n = 126) and quantitative descriptive analysis (QDA®) were used to describe the preparations. Physicochemical properties were also evaluated. When 50% and 75% cocoa powder was replaced with dry jackfruit seed flour, there was no change in sensory acceptability or technological properties; however, it is possible to identify advantages tousing dry jackfruit seed flour, including moisture reduction and high wettability, solubility and sensory acceptation of the chocolate aroma. The principal component analysis of QDA explained90% variances; cluster analysis enabled the definition of four groups for six cappuccino preparations. In fact, dry jackfruit seed flour is an innovative cocoa powder substitute; it could be used in food preparations, consequently utilizing this tropical fruit waste by incorporating it as an ingredient in a common product of the human diet.

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<![CDATA[Characterization of a Polyethylene Glycol-Amphotericin B Conjugate Loaded with Free AMB for Improved Antifungal Efficacy]]> https://www.researchpad.co/article/5989da70ab0ee8fa60b94b50

Amphotericin B (AMB) is a highly hydrophobic antifungal, whose use is limited by its toxicity and poor solubility. To improve its solubility, AMB was reacted with a functionalized polyethylene glycol (PEG), yielding soluble complex AmB-PEG formulations that theoretically comprise of chemically conjugated AMB-PEG and free AMB that is physically associated with the conjugate. Reverse-phase chromatography and size exclusion chromatography methods using HPLC were developed to separate conjugated AMB-PEG and free AmB, enabling the further characterization of these formulations. Using HPLC and dynamic light scattering analyses, it was observed that the AMB-PEG 2 formulation, having a higher molar ratio of 2 AMB: 1 PEG, possesses more free AMB and has relatively larger particle diameters compared to the AMB-PEG 1 formulation, that consists of 1 AMB: 1 PEG. The identity of the conjugate was also verified using mass spectrometry. AMB-PEG 2 demonstrates improved antifungal efficacy relative to AMB-PEG 1, without a concurrent increase in in vitro toxicity to mammalian cells, implying that the additional loading of free AMB in the AMB-PEG formulation can potentially increase its therapeutic index. Compared to unconjugated AMB, AMB-PEG formulations are less toxic to mammalian cells in vitro, even though their MIC50 values are comparatively higher in a variety of fungal strains tested. Our in vitro results suggest that AMB-PEG 2 formulations are two times less toxic than unconjugated AMB with antifungal efficacy on Candida albicans and Cryptococcus neoformans.

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<![CDATA[Highly porous regenerated cellulose hydrogel and aerogel prepared from hydrothermal synthesized cellulose carbamate]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc7e2

Here, a stable derivative of cellulose, called cellulose carbamate (CC), was produced from Kenaf (Hibiscus cannabinus) core pulp (KCP) and urea with the aid of a hydrothermal method. Further investigation was carried out for the amount of nitrogen yielded in CC as different urea concentrations were applied to react with cellulose. The effect of nitrogen concentration of CC on its solubility in a urea-alkaline system was also studied. Regenerated cellulose products (hydrogels and aerogels) were fabricated through the rapid dissolution of CC in a urea-alkaline system. The morphology of the regenerated cellulose products was viewed under Field emission scanning electron microscope (FESEM). The transformation of allomorphs in regenerated cellulose products was examined by X-ray diffraction (XRD). The transparency of regenerated cellulose products was determined by Ultraviolet–visible (UV–Vis) spectrophotometer. The degree of swelling (DS) of regenerated cellulose products was also evaluated. This investigation provides a simple and efficient procedure of CC determination which is useful in producing regenerated CC products.

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<![CDATA[Discovery of Novel Orally Active Tetrahydro-Naphthyl-N-Acylhydrazones with In Vivo Anti-TNF-α Effect and Remarkable Anti-Inflammatory Properties]]> https://www.researchpad.co/article/5989da21ab0ee8fa60b7eed6

LASSBio-1524 was designed as inhibitor of the IKK-β (kappa β kinase inhibitor) enzyme, which participates in the activation of the nuclear factor κB (NF-κB) canonical pathway, and its three N-acylhydrazone new analogues, LASSBio-1760, LASSBio-1763 and LASSBio-1764 are now being tested on their anti-inflammatory potential. The activity of these compounds was evaluated with the subcutaneous air pouch induced by carrageenan and by subsequent measurement of tumor necrosis factor-α (TNF-α), nitric oxide (NO) and reactive oxygen species (ROS). In the acute inflammation model, the oral pretreatment with doses from 0.3 to 30 mg/kg of N-acylhydrazone derivatives was able to significantly reduce leukocyte migration to the cavity. Pretreatment with LASSBio-1524 and its analogues also decreased NO, TNF-α and ROS biosynthesis an events closely involved with NF-kB pathway. The tetrahydronaphthyl-N-acylhydrazone derivative LASSBio-1764 was the most promising compound from this series, surpassing even LASSBio-1524. Additionally, none of the compounds demonstrated myelotoxicity or cytotoxicity. Cell viability was assayed and these compounds demonstrated to be safe at different concentrations. Western blot analysis demonstrated that LASSBio-1524 and LASSBio-1760 inhibited NF-κB expression in RAW 264.7 cell lineage. Our data indicate that the tested compounds have anti-inflammatory activity, which may be related to inhibition of leukocyte migration, reducing the production of NO, TNF-α and ROS. LASSBio-1524 and LASSBio-1760, in addition to these features, also reduced p65 nuclear expression assessed by western blot in RAW 264.7 murine cells.

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<![CDATA[Preformulation Studies on Piperlongumine]]> https://www.researchpad.co/article/5989daf8ab0ee8fa60bc3ab4

Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values ≥ 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media.

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<![CDATA[A Model for Dimerization of the SOX Group E Transcription Factor Family]]> https://www.researchpad.co/article/5989d9edab0ee8fa60b6d41d

Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG) domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

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<![CDATA[Properties of the cuticular proteins of Anopheles gambiae as revealed by serial extraction of adults]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc99b

How cuticular proteins (CPs) interact with chitin and with each other in the cuticle remains unresolved. We employed LC-MS/MS to identify CPs from 5–6 day-old adults of Anopheles gambiae released after serial extraction with PBS, EDTA, 2-8M urea, and SDS as well as those that remained unextracted. Results were compared to published data on time of transcript abundance, localization of proteins within structures and within the cuticle, as well as properties of individual proteins, length, pI, percent histidine, tyrosine, glutamine, and number of AAP[A/V/L] repeats. Thirteen proteins were solubilized completely, all were CPRs, most belonging to the RR-1 group. Eleven CPs were identified in both soluble fractions and the final pellet, including 5 from other CP families. Forty-three were only detected from the final pellet. These included CPRs and members of the CPAP1, CPF, CPFL, CPLCA, CPLCG, CPLCP, and TWDL families, as well as several low complexity CPs, not assigned to families and named CPLX. For a given protein, many histidines or tyrosines or glutamines appear to be potential participants in cross-linking since we could not identify any peptide bearing these residues that was consistently absent. We failed to recover peptides from the amino-terminus of any CP. Whether this implicates that location in sclerotization or some modification that prevents detection is not known. Soluble CPRs had lower isoelectric points than those that remained in the final pellet; most members of other CP families had isoelectric points of 8 or higher. Obviously, techniques beyond analysis of differential solubility will be needed to learn how CPs interact with each other and with chitin.

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<![CDATA[Sustained Antibiotic-Eluting Intra-Ocular Lenses: A New Approach]]> https://www.researchpad.co/article/5989da10ab0ee8fa60b794f6

Currently, infections following cataract surgery are not as effectively managed with antibiotic eye drops, which suffer from poor bioavailability of drug and low patient compliance. The ideal solution, which can help to overcome the issue of drug wastage and poor bioavailabilty, as well as the need for frequent applications (patient inconvenience), is a drug-eluting intraocular lens (IOL). We describe a novel approach to such a drug-eluting lens by using a peripheral IOL attachment as a drug depot to deliver antibiotics, Levofloxacin (LFX) or Moxifloxacin (MFX). In this work, drug was entrapped within a fully-degradable polymer, poly(L-lactide-co-ɛ-caprolactone) (PLC). The effects of drug loading and solvent type on drug release and film morphology were investigated using cast films. The study clearly demonstrated that a slower-evaporating solvent tetrahydrofuran (THF) resulted in a better surface morphology, as well as lower initial burst compared to dichloromethane (DCM), and hence, was better suited to developing a drug-eluting attachment with sustained release of drug. When attachments were fabricated with drugs at high loading percentages (20% and 25% in polymer), significant burst was observed compared to films: this is attributed to the higher surface-to-volume ratio of the attachments. When the levofloxacin (LFX) loading percentage was decreased to 3% and 5%, the attachments presented lower burst and sustained release with therapeutic efficacy. This work has demonstrated the potential of using an IOL attachment as a more efficacious anti-infective option compared to daily eye drops.

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<![CDATA[Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3]]> https://www.researchpad.co/article/5989d9f6ab0ee8fa60b70572

The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria.

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<![CDATA[Deciphering Mode of Action of Functionally Important Regions in the Intrinsically Disordered Paxillin (Residues 1-313) Using Its Interaction with FAT (Focal Adhesion Targeting Domain of Focal Adhesion Kinase)]]> https://www.researchpad.co/article/5989db17ab0ee8fa60bcd77c

Intrinsically disordered proteins (IDPs) play a major role in various cellular functions ranging from transcription to cell migration. Mutations/modifications in such IDPs are shown to be associated with various diseases. Current strategies to study the mode of action and regulatory mechanisms of disordered proteins at the structural level are time consuming and challenging. Therefore, using simple and swift strategies for identifying functionally important regions in unstructured segments and understanding their underlying mechanisms is critical for many applications. Here we propose a simple strategy that employs dissection of human paxillin (residues 1–313) that comprises intrinsically disordered regions, followed by its interaction study using FAT (Focal adhesion targeting domain of focal adhesion kinase) as its binding partner to retrace structural behavior. Our findings show that the paxillin interaction with FAT exhibits a masking and unmasking effect by a putative intra-molecular regulatory region. This phenomenon suggests how cancer associated mutations in paxillin affect its interactions with Focal Adhesion Kinase (FAK). The strategy could be used to decipher the mode of regulations and identify functionally relevant constructs for other studies.

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<![CDATA[Symmetry based assembly of a 2 dimensional protein lattice]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc8d4

The design of proteins that self-assemble into higher order architectures is of great interest due to their potential application in nanotechnology. Specifically, the self-assembly of proteins into ordered lattices is of special interest to the field of structural biology. Here we designed a 2 dimensional (2D) protein lattice using a fusion of a tandem repeat of three TelSAM domains (TTT) to the Ferric uptake regulator (FUR) domain. We determined the structure of the designed (TTT-FUR) fusion protein to 2.3 Å by X-ray crystallographic methods. In agreement with the design, a 2D lattice composed of TelSAM fibers interdigitated by the FUR domain was observed. As expected, the fusion of a tandem repeat of three TelSAM domains formed 21 screw axis, and the self-assembly of the ordered oligomer was under pH control. We demonstrated that the fusion of TTT to a domain having a 2-fold symmetry, such as the FUR domain, can produce an ordered 2D lattice. The TTT-FUR system combines features from the rotational symmetry matching approach with the oligomer driven crystallization method. This TTT-FUR fusion was amenable to X-ray crystallographic methods, and is a promising crystallization chaperone.

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<![CDATA[Stability of gabapentin in extemporaneously compounded oral suspensions]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc756

This study reports the stability of extemporaneously prepared gabapentin oral suspensions prepared at 100 mg/mL from bulk drug and capsules in either Oral Mix or Oral Mix SF suspending vehicles. Suspensions were packaged in amber plastic bottles and amber plastic syringes at 25°C / 60%RH for up to 90 days. Throughout the study period, the following tests were performed to evaluate the stability of the preparations: organoleptic inspection to detect homogeneity, color or odor changes; pH measurements; and gabapentin assay using a stability-indicating HPLC-UV method. As crystallization was observed at 5°C, storage at this temperature condition is not recommended. All preparations stored at 25°C / 60%RH remained stable for the whole study duration of 90 days.

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<![CDATA[Expression of Functional Human Sialyltransferases ST3Gal1 and ST6Gal1 in Escherichia coli]]> https://www.researchpad.co/article/5989db47ab0ee8fa60bd8c7a

Sialyltransferases (STs) are disulfide-containing, type II transmembrane glycoproteins that catalyze the transfer of sialic acid to proteins and lipids and participate in the synthesis of the core structure oligosaccharides of human milk. Sialic acids are found at the outermost position of glycostructures, playing a key role in health and disease. Sialylation is also essential for the production of recombinant therapeutic proteins (RTPs). Despite their importance, availability of sialyltransferases is limited due to the low levels of stable, soluble and active protein produced in bacterial expression systems, which hampers biochemical and structural studies on these enzymes and restricts biotechnological applications. We report the successful expression of active human sialyltransferases ST3Gal1 and ST6Gal1 in commercial Escherichia coli strains designed for production of disulfide-containing proteins. Fusion of hST3Gal1 with different solubility enhancers and substitution of exposed hydrophobic amino acids by negatively charged residues (supercharging-like approach) were performed to promote solubility and folding. Co-expression of sialyltransferases with the chaperon/foldases sulfhydryl oxidase, protein disulfide isomerase and disulfide isomerase C was explored to improve the formation of native disulfide bonds. Active sialyltransferases fused with maltose binding protein (MBP) were obtained in sufficient amounts for biochemical and structural studies when expressed under oxidative conditions and co-expression of folding factors increased the yields of active and properly folded sialyltransferases by 20%. Mutation of exposed hydrophobic amino acids increased recovery of active enzyme by 2.5-fold, yielding about 7 mg of purified protein per liter culture. Functionality of recombinant enzymes was evaluated in the synthesis of sialosides from the β-d-galactoside substrates lactose, N-acetyllactosamine and benzyl 2-acetamido-2-deoxy-3-O-(β-d-galactopyranosyl)-α-d-galactopyranoside.

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<![CDATA[Yellow Mealworm Protein for Food Purposes - Extraction and Functional Properties]]> https://www.researchpad.co/article/5989da90ab0ee8fa60b9fd41

A protocol for extraction of yellow mealworm larvae proteins was established, conditions were evaluated and the resulting protein extract was characterised. The freeze-dried yellow mealworm larvae contained around 33% fat, 51% crude protein and 43% true protein on a dry matter basis. The true protein content of the protein extract was about 75%, with an extraction rate of 70% under optimised extraction conditions using 0.25 M NaOH, a NaOH solution:ethanol defatted worm ratio of 15:1 mL/g, 40°C for 1 h and extraction twice. The protein extract was a good source of essential amino acids. The lowest protein solubility in distilled water solution was found between pH 4 and 5, and increased with either increasing or decreasing pH. Lower solubility was observed in 0.5 M NaCl solution compared with distilled water. The rheological tests indicated that temperature, sample concentration, addition of salt and enzyme, incubation time and pH alterations influenced the elastic modulus of yellow mealworm protein extract (YMPE). These results demonstrate that the functional properties of YMPE can be modified for different food applications.

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<![CDATA[Release of Si from Silicon, a Ferrosilicon (FeSi) Alloy and a Synthetic Silicate Mineral in Simulated Biological Media]]> https://www.researchpad.co/article/5989d9e6ab0ee8fa60b6b43b

Unique quantitative bioaccessibility data has been generated, and the influence of surface/material and test media characteristics on the elemental release process were assessed for silicon containing materials in specific synthetic body fluids at certain time periods at a fixed loading. The metal release test protocol, elaborated by the KTH team, has previously been used for classification, ranking, and screening of different alloys and metals. Time resolved elemental release of Si, Fe and Al from particles, sized less than 50 µm, of two grades of metallurgical silicon (high purity silicon, SiHG, low purity silicon, SiLG), an alloy (ferrosilicon, FeSi) and a mineral (aluminium silicate, AlSi) has been investigated in synthetic body fluids of varying pH, composition and complexation capacity, simple models of for example dermal contact and digestion scenarios. Individual methods for analysis of released Si (as silicic acid, Si(OH)4) in synthetic body fluids using GF-AAS were developed for each fluid including optimisation of solution pH and graphite furnace parameters. The release of Si from the two metallurgical silicon grades was strongly dependent on both pH and media composition with the highest release in pH neutral media. No similar effect was observed for the FeSi alloy or the aluminium silicate mineral. Surface adsorption of phosphate and lactic acid were believed to hinder the release of Si whereas the presence of citric acid enhanced the release as a result of surface complexation. An increased presence of Al and Fe in the material (low purity metalloid, alloy or mineral) resulted in a reduced release of Si in pH neutral media. The release of Si was enhanced for all materials with Al at their outermost surface in acetic media.

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<![CDATA[Copper and Zinc Interactions with Cellular Prion Proteins Change Solubility of Full-Length Glycosylated Isoforms and Induce the Occurrence of Heterogeneous Phenotypes]]> https://www.researchpad.co/article/5989d9eeab0ee8fa60b6da60

Prion diseases are characterized biochemically by protein aggregation of infectious prion isoforms (PrPSc), which result from the conformational conversion of physiological prion proteins (PrPC). PrPC are variable post-translationally modified glycoproteins, which exist as full length and as aminoterminally truncated glycosylated proteins and which exhibit differential detergent solubility. This implicates the presence of heterogeneous phenotypes, which overlap as protein complexes at the same molecular masses. Although the biological function of PrPC is still enigmatic, evidence reveals that PrPC exhibits metal-binding properties, which result in structural changes and decreased solubility. In this study, we analyzed the yield of PrPC metal binding affiliated with low solubility and changes in protein banding patterns. By implementing a high-speed centrifugation step, the interaction of zinc ions with PrPC was shown to generate large quantities of proteins with low solubility, consisting mainly of full-length glycosylated PrPC; whereas unglycosylated PrPC remained in the supernatants as well as truncated glycosylated proteins which lack of octarepeat sequence necessary for metal binding. This effect was considerably lower when PrPC interacted with copper ions; the presence of other metals tested exhibited no effect under these conditions. The binding of zinc and copper to PrPC demonstrated differentially soluble protein yields within distinct PrPC subtypes. PrPC–Zn2+-interaction may provide a means to differentiate glycosylated and unglycosylated subtypes and offers detailed analysis of metal-bound and metal-free protein conversion assays.

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<![CDATA[Antioxidant Activity and α-Glucosidase Inhibitory Activities of the Polycondensate of Catechin with Glyoxylic Acid]]> https://www.researchpad.co/article/5989da81ab0ee8fa60b9a857

In order to investigate polymeric flavonoids, the polycondensate of catechin with glyoxylic acid (PCG) was prepared and its chemically antioxidant, cellular antioxidant (CAA) and α-glucosidase inhibitory activities were evaluated. The DPPH and ABTS radical scavenging activities and antiproliferative effect of PCG were lower than those of catechin, while PCG had higher CAA activity than catechin. In addition, PCG had very high α-glucosidase inhibitory activities (IC50 value, 2.59 μg/mL) in comparison to catechin (IC50 value, 239.27 μg/mL). Inhibition kinetics suggested that both PCG and catechin demonstrated a mixture of noncompetitive and anticompetitive inhibition. The enhanced CAA and α-glucosidase inhibitor activities of PCG could be due to catechin polymerization enhancing the binding capacity to the cellular membrane and enzymes.

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<![CDATA[Design, synthesis and structure-activity relationship study of wollamide B; a new potential anti TB agent]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdc9d4

Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness. Among the 25 synthesized wollamides five of them showed potent activities with MICs ≤ 3.1 μM and found to be nontoxic against human HepG2 cells up to 100 μM. The results of the in vitro ADME profiling revealed the remarkable plasma stability and very good aqueous solubility of the class in general while the metabolic stability was found to be moderate to low. Of particular note, compounds 7c (MIC = 1.1 μM) and 13c (0.6 μM) that exhibited good balance of antimycobacterial activity vs. optimal pharmacokinetic properties could be used as a new lead for further development.

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