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Nanocarriers as an Emerging Platform for Cancer Therapy
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Dan Peer, Jeffrey M. Karp, Seungpyo Hong, Omid C. Farokhzad, Rimona Margalit, Robert Langer
It is also possible to increase binding affinity and selectivity to cell surface targets by engineering proteins that detect a specific conformation of a target receptor. In a recent in vivo study using a fusion protein consisting of an scFv antibody fragment to target and deliver small interfering RNA (siRNA) to lymphocytes—a type of white blood cell—a 10,000-fold increased affinity for the target receptor, integrin LFA-1, was observed [18]. Integrin LFA-1 is usually present in a low-affinity non-adhesive form on na¨ıve leukocytes (white blood cells that are not activated by cancer cells or pathogens that enter the body), but converts to the high-affinity adhesive form through conformational changes on activation of the immune system. Therefore, targeting the high-affinity form of LFA-1 enables drugs to be selectively delivered to the activated and adhesive leukocytes. New classes of targeting molecules can be engineered to target specific conformations. These include small protein domains, known as affibodies, that can be engineered to bind specifically to different target proteins in a conformational-sensitive manner. Other small proteins that act like antibodies—called avimers—are used to bind selectively to target receptors through multivalent effects. Nanobodies, which are heavy-chain antibodies engineered to one tenth of the size of an intact antibody with a missing light chain, have been used to bind to carcinoembryonic antigen (CEA), a protein used as a tumour marker [38–40] (Fig. 2.2b).
Genetically Engineered Protein Domains as Hydrogel Crosslinks
Published in Raphael M. Ottenbrite, Sung Wan Kim, Polymeric Drugs & Drug Delivery Systems, 2019
Chun Wang, Russell J. Stewart, Russell J. Stewart, Jindrich KopeČek
One unique feature of our design is the use of coiled-coil protein domains. In addition to temperature-induced volume transition and responsiveness to chelating agents, sensitivity toward other stimuli, such as pH, ionic strength, solvents, electric current, mechanical force, or specific recognition and binding with ligand, could also be built into the hydrogel system. This could be accomplished by incorporating protein domains with specially engineered sequences. Furthermore, certain physical properties of the hydrogels, such as viscosity, gelation temperature, elasticity, rigidity, porosity, and bioerodibility, can be similarly tailored. As one of the possible extensions of the work described here, all the “e” and “g” positions of the heptad repeats of a coiled-coil strand could be occupied by glutamic acid or by lysine residues. Electrostatic interaction between two of such strands would favor specific formation of a heterodimer. Polar residues, such as as-paragine, could be inserted at the hydrophobic interface to facilitate specific alignment and orientation of the two strands and to decrease overall stability. Compared with the hybrid hydrogels formed using TEK42 as crosslinkers, gels crosslinked by such heterodimeric coiled-coil domains would be expected to have better defined pore size, better crosslinking efficiency with less intramolecular crosslinker, and a lower dissociation temperature.
Trends in Biotechnology
Published in Firdos Alam Khan, Biotechnology Fundamentals, 2020
A protein domain is a conserved part of a given protein sequence and (tertiary) structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. The shortest domains such as zinc fingers are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be swapped by genetic engineering between one protein and another to make chimeric proteins. The primary goal of bioinformatics is to increase the understanding of biological processes. What sets it apart from other methods, however, is its focus on developing and applying computationally intensive techniques such as pattern recognition, data mining, machine learning algorithms, and visualization to achieve this goal. Major research efforts in the field include sequence alignment, gene finding, genome assembly, drug design, drug discovery, protein structure alignment, protein structure prediction, prediction of gene expression and protein–protein interactions, genome-wide association studies, the modeling of evolution and cell division/mitosis. Based on the application of biological data, bioinformatics is classified into various sub-types, which are discussed as below:
Evaluation of a peptide motif designed for protein tethering to polymer surfaces
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Ayana Nakano, Isao Hirata, Binh Vinh Pham, Ajay Shakya, Kotaro Tanimoto, Koichi Kato
To gain insights into the 3 D structure of the KL5-fused proteins, ab initio structure prediction was performed for EGF-KL5-His, bFGF-KL5-His, and SDF-1α-KL5-His. Figure 1 shows the most probable models predicted for these proteins. As shown in Figure 1(a), the KL5 peptides tended to form different secondary structures depending on the protein partners: β-strand in EGF-KL5-His, coil in bFGF-KL5-His, and α-helix in SDF-1α-KL5-His. These results suggest that the protein domains have influences on the structure of KL5. However, it was predicted that the KL5 peptide is exposed to the outside of all the fusion proteins (Figure 1(b)), which seems to be advantageous for the accessibility of the peptide. In addition, the secondary structure distribution along each protein sequence in the fusions was generally similar to that found in the crystal structure of wild-type counterparts [19–21], suggesting that the structure of the protein domains is not substantially affected by the fusion of KL5. Although slight alterations were seen in the secondary structure of the protein domain in the fusions compared to the wild-type, it is unknown whether they are due to the fusion of KL5 or the uncertainty of the predictions.
The influence of polycyclic aromatic hydrocarbons in protein profile of Medicago sativa L.
Published in International Journal of Phytoremediation, 2021
Wilber S. Alves, Noemi S. Santos, Felipe F. Baroca, Bruna P. D. Alves, Rosane O. Nunes, Giselli C. D. Abrahão, Evelin A. Manoel, Marcia R. Soares
We also identified two proteins related with alcohol dehydrogenase domain, this proteins are uncharacterized protein LOC11443106 (with a alcohol dehydrogenase-like protein domain) and 2-methylene-furan-3-one reductase (with a MDR-LIKE-2 domain), this proteins are belong to the medium-chain dehydrogenases/reductases (MDR) superfamily which has almost 1000 members spread in all types of organisms and the transcription of this proteins in plants has been demonstrated to increase by environmental stress (Thompson et al. 2010) and also be classified in macrofamilies I and II include the zinc-containing MDRs (Knoll and Pleiss 2008). In “green liver” concept, plants appear to contain isoenzymes with specificity for secondary plant substrates or xenobiotics, some of them acting like progenitors of plant alcohol dehydrogenase superfamily (Sandermann 1999). In plants, alcohol dehydrogenase (ADH, EC1.1.1.1) is a key enzyme responsible for catalyzing the reduction of acetaldehyde to ethanol using NADH as reductant, especially during the periods of anaerobic stress (Shi et al. 2017). And 2-methylene-furan-3-one reductase can reduced artificial substrate 9,10-phenanthrenequinone (Klein et al. 2007). According to KEGG classification, alcohol dehydrogenases could act in the degradation pathways toxic aromatic compounds, such naphthalene (ko00626), 1-methylnaphthalene and 2-methylnaphthalene (ko01220). Along with alcohol dehydrogenase, we identified another dehydrogenase (acyl-CoA dehydrogenase), which was classified as a protein related to the metabolism and degradation of xenobiotics. This participates in the benzoate degradation pathway (ko00362).
Natural latex serum: characterization and biocompatibility assessment using Galleria mellonella as an alternative in vivo model
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Giovana Sant’Ana Pegorin Brasil, Patrícia Pimentel de Barros, Matheus Carlos Romeiro Miranda, Natan Roberto de Barros, Juliana Campos Junqueira, Alejandro Gomez, Rondinelli Donizetti Herculano, Ricardo José de Mendonça
Antigen recognition by antibody involves non-covalent reversible bonds of the variable fraction of the antibody with specific parts of the antigenic macromolecule, called epitopes [81]. Thus, this result confirms the presence of a protein domain that serves as an epitope for the interaction with this antibody, specific anti-FGFb, and can help explain the mechanism of action of the material on cell multiplication and angiogenesis.