Protein nanoparticles directed cancer imaging and therapy

Cancer has been a serious threat to human health. Among drug delivery carriers, protein nanoparticles are unique because of their mild and environmentally friendly preparation methods. They also inherit desired characteristics from natural proteins, such as biocompatibility and biodegradability. Therefore, they have solved some problems inherent to inorganic nanocarriers such as poor biocompatibility. Also, the surface groups and cavity of protein nanoparticles allow for easy surface modification and drug loading. Besides, protein nanoparticles can be combined with inorganic nanoparticles or contrast agents to form multifunctional theranostic platforms. This review introduces representative protein nanoparticles applicable in cancer theranostics, including virus-like particles, albumin nanoparticles, silk protein nanoparticles, and ferritin nanoparticles. It also describes the common methods for preparing them. It then critically analyzes the use of a variety of protein nanoparticles in improved cancer imaging and therapy.

Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A

Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC50 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC50 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved.

In silico analysis of phylogeny, structure, and function of arsenite oxidase from unculturable microbiome of arsenic contaminated soil

Background Arsenite oxidase (EC 1.20.2.1) is a metalloenzyme that catalyzes the oxidation of arsenite into lesser toxic arsenate. In this study, 78 amino acid sequences of arsenite oxidase from unculturable bacteria available in metagenomic data of arsenic-contaminated soil have been characterized by using standard bioinformatics tools to investigate its phylogenetic relationships, three-dimensional structure and functional parameters. Results The phylogenetic relationship of all arsenite oxidase from unculturable microorganisms was revealed their closeness to bacterial order Rhizobiales. The higher aliphatic content showed that these enzymes are thermostable and could be used for in situ bioremediation. A representative protein from each phylogenetic cluster was analysed for secondary structure arrangements which indicated the presence of α-helices (~63%), β-sheets (57–60%) and turns (13–15%). The validated 3D models suggested that these proteins are hetero-dimeric with two chains whereas alpha chain is the main catalytic subunit which binds with arsenic oxides. Three representative protein models were deposited in Protein Model Database. The query enzymes were predicted with two conserved motifs, one is Rieske 3Fe-4S and the other is molybdopterin protein. Conclusions Computational analysis of protein interactome revealed the protein partners might be involved in the whole process of arsenic detoxification by Rhizobiales. The overall report is unique to the best of our knowledge, and the importance of this study is to understand the theoretical aspects of the structure and functions of arsenite oxidase in unculturable bacteria residing in arsenic-contaminated sites.

Genome3D: integrating a collaborative data pipeline to expand the depth and breadth of consensus protein structure annotation

Genome3D (https://www.genome3d.eu) is a freely available resource that provides consensus structural annotations for representative protein sequences taken from a selection of model organisms. Since the last NAR update in 2015, the method of data submission has been overhauled, with annotations now being ‘pushed’ to the database via an API. As a result, contributing groups are now able to manage their own structural annotations, making the resource more flexible and maintainable. The new submission protocol brings a number of additional benefits including: providing instant validation of data and avoiding the requirement to synchronise releases between resources. It also makes it possible to implement the submission of these structural annotations as an automated part of existing internal workflows. In turn, these improvements facilitate Genome3D being opened up to new prediction algorithms and groups. For the latest release of Genome3D (v2.1), the underlying dataset of sequences used as prediction targets has been updated using the latest reference proteomes available in UniProtKB. A number of new reference proteomes have also been added of particular interest to the wider scientific community: cow, pig, wheat and mycobacterium tuberculosis. These additions, along with improvements to the underlying predictions from contributing resources, has ensured that the number of annotations in Genome3D has nearly doubled since the last NAR update article. The new API has also been used to facilitate the dissemination of Genome3D data into InterPro, thereby widening the visibility of both the annotation data and annotation algorithms.

Evaluation of Protein Adsorption Capacity of TiO2-Supported Spherical Porous Hydroxyapatite

In this study, a novel titania-supported spherical porous hydroxyapatite (sHAp + TiO2) was prepared by compounding minute, uniquely shaped spherical porous hydroxyapatites (sHAp) with TiO2. Adsorption of the representative protein bovine serum albumin (BSA) was evaluated and simulated body fluid immersion experiments were carried out. Minimal adsorption of BSA to TiO2 was observed, and 33% and 25% adsorption to sHAp + TiO2 and sHAp were observed, respectively. The reduction in BSA concentration observed in the sHAp and sHAp + TiO2 solutions is presumably due to adsorption to HAp. It is highly likely that adsorption of the acidic protein BSA occurred at the sHAp Ca2+ site. In the simulated body fluid immersion experiments, there was greater expression of hydroxyapatite (HAp) on the surface of sHAp than there was on the surface of sHAp + TiO2. In the case of TiO2 alone, no HAp was produced, even after immersion for 3 days. These results suggest a relationship between BSA adsorption and the osteoconductivity of materials.

Selection of DNA aptamers with two modified bases

The nucleobases comprising DNA and RNA aptamers provide considerably less chemical diversity than protein-based ligands, limiting their versatility. The introduction of novel functional groups at just one of the four bases in modified aptamers has recently led to dramatic improvement in the success rate of identifying nucleic acid ligands to protein targets. Here we explore the benefits of additional enhancement in physicochemical diversity by selecting modified DNA aptamers that contain amino-acid–like modifications on both pyrimidine bases. Using proprotein convertase subtilisin/kexin type 9 as a representative protein target, we identify specific pairwise combinations of modifications that result in higher affinity, metabolic stability, and inhibitory potency compared with aptamers with single modifications. Such doubly modified aptamers are also more likely to be encoded in shorter sequences and occupy nonoverlapping epitopes more frequently than aptamers with single modifications. These highly modified DNA aptamers have broad utility in research, diagnostic, and therapeutic applications.

Toxicity of chlorpyrifos on protease and glutamate dehydrogenase enzyme activities in albino rats

Present study was aimed to elucidate the pesticide toxicity in rats involves induced abnormalities of the intracellular protein catabolic process by the effect of one of the commonly used organophosphate compound chlorpyrifos on the activities of representative protein catabolising proteases and Glutamate dehydrogenase (GDH) is a one of the regulatory enzyme known to check the deamination process to minimize the ammonia level and plays a significant role in the catabolism of amino acids. The sub lethal stress of chlorpyrifos on important metabolites and enzymes of protein metabolism was investigated in most important tissues like liver, kidney, heart and intestine of albino rats. Sub lethal concentration (1/10th LD50 i.e., 20mg/kg body weight) of chlorpyrifos (Organophosphate) on the enzyme parameters of albino rats were analysed after single, double and multiple dose of exposure. The increased protease activities in the different tissues of rat indicate the damage caused due to impairment of energy supply and proteases activity indicates higher protein degradation. Therefore, the proteins are denatured leading to more activation of proteases. The elevated GDH activity levels indicate its contribution to ammonia production and glutamate oxidation during chlorpyrifos toxicity.

Magnetically-actuated, bead-enhanced silicon photonic immunosensor

Magnetic actuation has been introduced to an optical immunosensor technology resulting in improvements in both rapidity and limit of detection for an assay quantitating low concentrations of a representative protein biomarker.

Immobilization of SA-α-2,6-Gal Receptors Related to Influenza on Magnetic Nanoparticles Coated with Chitosan

Influenza infection is carried out due to the virus hemagglutinin recognizes host cell surface with terminal sialic acid (SA) linked receptors SA-α-2,6-Gal for human strain. Sambucus nigra lectin has structural similarity to the viral hemagglutinin. Magnetic nanoparticles (MNP) coated with chitosan can be used as support for the study of these receptors. The goal of this study was to extract the SA-α-2,6-Gal receptors of porcine trachea for their immobilization on magnetic nanoparticles coated with chitosan. The extraction was carried out based on affinity of Sambucus nigra lectin to SA-α-2,6-Gal receptors. It was possible to immobilize up to 76% of SA-α-2,6-Gal receptors, with a molecular weight at 88.4 kDa for more representative protein. The presence of the receptors was confirmed trough FTIR analysis. Magnetic functionalized nanoparticles showed superparamagnetic properties and an average diameter around 10 nm. These results may be used to evaluate the interaction between functionalized nanoparticles and specific lectin or hemagglutinin of influenza virus as model of study virus-receptor.