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https://www.readbyqxmd.com/read/28339191/allosteric-activation-of-cytochrome-p450-3a4-via-progesterone-bioconjugation
#1
Vanja Polic, Karine Auclair
Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of the majority of drugs. As such, it is implicated in many adverse drug-drug and food-drug interactions, and is of significant interest to the pharmaceutical industry. This enzyme is known to simultaneously bind multiple ligands and display atypical enzyme kinetics, suggestive of allostery and cooperativity. As well, evidence of a postulated peripheral allosteric binding site has provoked debate around its significance and location. We report the use of bioconjugation to study the significance of substrate binding at the proposed allosteric site and its effect on CYP3A4 activity...
March 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28332258/n-terminal-chemical-protein-labeling-using-the-naturally-split-gos-terl-intein
#2
Anne-Lena Bachmann, Henning D Mootz
Chemoselective and regioselective chemical protein labeling is of great importance, yet no current technique is sufficiently general and simple to perform. Protein trans-splicing by split inteins can be used to ligate short tags with chemical labels to either the N or the C terminus of a protein. The CysTag approach exploits split intein fragments without a cysteine fused with such a short tag containing a single cysteine that is easily amenable to selective modification using classical cysteine bioconjugation...
March 23, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28328923/bioconjugation-methionine-s-time-to-shine
#3
Caitlin Deane
No abstract text is available yet for this article.
March 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28326226/comparison-of-four-methods-for-the-biofunctionalization-of-gold-nanorods-by-the-introduction-of-sulfhydryl-groups-to-antibodies
#4
Xuefeng Wang, Zhong Mei, Yanyan Wang, Liang Tang
Introducing sulfhydryl groups to biomolecules to functionalize gold nanorods (GNRs) is an attractive method that involves the creation of a strong Au-S bond. Previously, we developed a facile method to functionalize GNR surfaces by thiolating antibodies using Traut's reagent. In the current study, we evaluated several methods for the introduction of thiol groups onto the surface of GNRs by using Traut's reagent, dithiotreitol (DTT), dithiolaromatic PEG6-CONHNH2, and thiol-polyethylene glycolamine (SH-PEG-NH2) combined with EDC reaction...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28323116/the-effect-of-g3-pamam-dendrimer-conjugated-with-b-group-vitamins-on-cell-morphology-motility-and-atp-level-in-normal-and-cancer-cells
#5
Łukasz Uram, Magdalena Szuster, Maria Misiorek, Aleksandra Filipowicz, Stanisław Wołowiec, Elżbieta Wałajtys-Rode
In a search for the safe vitamin carrier the PAMAM G3 dendrimer covalently substituted with 9 and 10 molecules of vitamin B7 (biotin) and B6 (pyridoxal), respectively (BC-PAMAM) was investigated. Dendrimer substitution with B-group vitamins significantly alters its biological properties as compared to native form. Observed effects on investigated cell parameters including morphology, adhesion, migration and ATP level were different for normal human fibroblasts (BJ) and squamous cell carcinoma (SCC-15) cell lines...
March 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28316233/dna-linkers-and-diluents-for-ultrastable-gold-nanoparticle-bioconjugates-in-multiplexed-assay-development
#6
Samuel S Hinman, Kristy S McKeating, Quan Cheng
A novel bioconjugation strategy leading to ultrastable gold nanoparticles (AuNPs), utilizing DNA linkers and diluents in place of traditional self-assembled monolayers, is reported. The protective capacity of DNA confers straightforward biomolecular attachment and multistep derivatization capabilities to these nanoparticles and, more significantly, substantially enhances their stability in demanding and complex sensing environments. The DNA/AuNPs were assembled through pH-assisted thiol-gold bonding of single stranded DNA and salt aging, with preconjugated biotin moieties facing outward from the gold surface...
March 24, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28315359/antibodies-and-associates-partners-in-targeted-drug-delivery
#7
REVIEW
Patrick J Kennedy, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Monoclonal antibodies (mAbs) are well established in the clinic due to their specificity and affinity to a diverse array of biochemical targets. More recently, mAbs are being exploited as targeting agents in modern drug delivery systems, aiming to bypass normal host tissue and to accumulate a therapeutic agent to a specific tissue or cell for enhanced pharmacology. At sizes ranging from ~10-100nm, antibody-based bioconjugates have opened up a whole new realm of clinical possibilities with several platforms emerging on the market...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28304032/facile-synthesis-of-chlorin-bioconjugates-by-a-series-of-click-reactions
#8
Junior Gonzales, N V S Dinesh K Bhupathiraju, William Perea, Huong Chu, Naxhije Berisha, Veronica Bueno, Naser Dodic, Julia Rozenberg, Nancy L Greenbaum, Charles Michael Drain
A multifunctional chlorin platform appended with four short polyethylene glycols and a carboxylate-linker allows rapid conjugation to biotargeting motifs such as proteins and oligonucleotides. The stability and photophysical properties of the chlorin enable development of diagnostics, imaging, molecular tracking, and theranostics.
March 17, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28303322/super-sensitive-time-resolved-fluoroimmunoassay-for-thyroid-stimulating-hormone-utilizing-europium-iii-nanoparticle-labels-achieved-by-protein-corona-stabilization-short-binding-time-and-serum-preprocessing
#9
Tuomas Näreoja, Jessica M Rosenholm, Urpo Lamminmäki, Pekka E Hänninen
Thyrotropin or thyroid-stimulating hormone (TSH) is used as a marker for thyroid function. More precise and more sensitive immunoassays are needed to facilitate continuous monitoring of thyroid dysfunctions and to assess the efficacy of the selected therapy and dosage of medication. Moreover, most thyroid diseases are autoimmune diseases making TSH assays very prone to immunoassay interferences due to autoantibodies in the sample matrix. We have developed a super-sensitive TSH immunoassay utilizing nanoparticle labels with a detection limit of 60 nU L(-1) in preprocessed serum samples by reducing nonspecific binding...
March 16, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28302030/gold-nanoparticles-conjugated-levofloxacin-for-improved-antibacterial-activity-over-levofloxacin-alone
#10
Paramdeep Bagga, H H Siddiqui, Juber Akhtar, Tariq Mahmood, Manaal Zahera, Mohd Sajid Khan
Levofloxacin is a potent antibiotic with severe side effects due to its high doses. Bacterial resistance may be due to frequent use of antibiotics. Biogenic gold nanoparticles conjugated levofloxacin (Au-HSA-LvN-NPs) were developed by Human Serum Albumin (HSA) and sulfite reductase-mediated pathways. Au-HSA-LvN-NPs (size = 27.2 ± 1 nm) were readily generated with high emulsion stability zeta potential (̵13.3 mV). The developed nanoparticles were also characterized by UV-visible spectroscopy, Transmission Electron Microscopy and Dynamic Light Scattering techniques...
March 16, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28300392/generation-and-characterization-of-virus-infection-enhancing-peptide-nanofibrils-functionalized-with-fluorescent-labels
#11
Sascha Rode, Manuel Hayn, Annika Röcker, Stefanie Sieste, Marcus Lamla, Daniel Markx, Christoph Meier, Frank Kirchhoff, Paul Walther, Marcus Fändrich, Tanja Weil, Jan Muench
Retroviral gene transfer is the method of choice for the stable introduction of genetic material into the cellular genome. However, efficient gene transfer is often limited by low transduction rates of the viral vectors. We have recently described a 12-mer peptide, termed EF-C that forms amyloid-like peptide nanofibrils (PNF) strongly increasing viral transduction efficiencies. These nanofibrils are polycationic and bind negatively charged membranes of virions and cells, thereby overcoming charge repulsions and resulting in increased rates of virion attachment and gene transfer...
March 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28299901/dual-display-of-proteins-on-the-yeast-cell-surface-simplifies-quantification-of-binding-interactions-and-enzymatic-bioconjugation-reactions
#12
Sungwon Lim, Jeff E Glasgow, Maria Filsinger Interrante, Erica M Storm, Jennifer R Cochran
Yeast surface display, a well-established technology for protein analysis and engineering, involves expressing a protein of interest as a genetic fusion to either the N- or C-terminus of the yeast Aga2p mating protein. Historically, yeast-displayed protein variants are flanked by peptide epitope tags that enable flow cytometric measurement of construct expression using fluorescent primary or secondary antibodies. Here, we built upon this technology to develop a new yeast display strategy that comprises fusion of two different proteins to Aga2p, one to the N-terminus and one to the C-terminus...
March 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28289128/characterizing-the-overall-derivatization-of-conjugated-oligomeric-proteins
#13
Michaela Wendeler, Wei Zhao, Christopher Thompson, Manuel Baca, Dhanesh Gadre, Xiangyang Wang, Harry Yang
The analysis and accurate quantitation of bioconjugations proves challenging in the case of oligomeric proteins, especially when the size of the molecule or the nature of the conjugate do not allow the analysis of the intact protein under native conditions. In this case, analytical methods are frequently applied that result in a dissociation of non-covalently linked subunits. This limits the analysis to a description of individual subunits, thereby obscuring the accurate characterization of the overall functionalization...
March 13, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/28286038/multi-stimuli-responsive-biohybrid-nanoparticles-with-cross-linked-albumin-coronae-self-assembled-by-a-polymer-protein-biodynamer
#14
Lin Wang, Li Liu, Bingyang Dong, Hanying Zhao, Mingming Zhang, Wenjuan Chen, Yanhang Hong
A thermoresponsive polymer-protein biodynamer was prepared via the bioconjugation of an aliphatic aldehyde-functionalized copolymer to hydrazine-modified bovine serum albumin (BSA) through reversible pyridylhydrazone linkages. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography (SEC) results indicated that the pyridylhydrazone linkages cleaved in an intracellular-mimicking acidic milieu, thus leading to the release of BSA. The dynamic character of the protein biodynamer was demonstrated by exchange reactions with aldehyde-containing molecules...
March 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28273560/overcoming-drug-resistance-by-cell-penetrating-peptide-mediated-delivery-of-a-doxorubicin-dimer-with-high-dna-binding-affinity
#15
Marco Lelle, Christoph Freidel, Stefka Kaloyanova, Ilja Tabujew, Alexander Schramm, Michael Musheev, Christof Niehrs, Klaus Müllen, Kalina Peneva
We describe the synthesis and characterization of a novel bioconjugate, consisting of an octaarginine cell-penetrating peptide and a highly DNA-affine doxorubicin dimer. The linkage between the two components is composed of a cleavable disulfide bond, which enables the efficient intracellular delivery of the cytotoxic payload within the reductive environment of the cytosol, mediated through glutathione. To determine the DNA-binding affinity of the dimeric drug molecule, microscale thermophoresis was applied...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28270086/therapeutic-implications-of-superoxide-dismutase-and-its-importance-inkinase-drug-discovery
#16
Monalisa Mukherjee, Satyendra K Rajput, Deepa Suhag, Apoorv Gupta, Aarti Singh, Vipin Kumar, Adeeba Shakeel, Arun Kumar Sharma, Nameet Kaur
In recent years, several scientific investigations have reported the therapeutic implications of superoxide dismutase (SOD) against oxidative stress and -induced pathology in clinical and preclinical trials. Indeed, various kinase, molecular signaling and physiological process has altered by reactive oxygen species. In spite of the abundant available literature reports, patents, clinical trials and commercialized products, the therapeutic application of SOD as a potential drug still remains unclear. Owing to the technical challenges associated with the utilization of SOD as a drug, we revisited the structural arrangement and cellular signaling, significant association with kinase which exploring the new target sites and introduction of new formulation strategies such as gene modulation, nano-formulations and click chemistry is a prerequisite...
March 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28267922/tetrazine-trans-cyclooctene-mediated-conjugation-of-antibodies-to-microtubules-facilitates-subpicomolar-protein-detection
#17
Samata Chaudhuri, Till Korten, Stefan Diez
Engineering cargo-loading strategies is crucial to developing nanotechnological applications of microtubule-based biomolecular transport systems. Here, we report a highly efficient and robust bioconjugation scheme to load antibodies to microtubules. Our method takes advantage of the inverse-electron-demand Diels-Alder addition reaction between tetrazine and trans-cyclooctene: the fastest known bioorthogonal reaction, characterized by its excellent selectivity and biocompatibility. As proof of concept, we performed kinesin-1 gliding motility assays with antibody-conjugated microtubules and demonstrated the highly sensitive detection of fluorescent protein analyte down to 0...
March 14, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28263563/alkyne-functionalized-coumarin-compound-for-analytic-and-preparative-4-thiouridine-labeling
#18
Katharina Schmid, Maria Adobes-Vidal, Mark Helm
Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on posttranscriptional modification. This work focusses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA, and is used as a metabolic label and for crosslinking purposes in eukaryotic RNA. A newly designed coumarin compound, named 7-propargyloxy-4-bromomethylcoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via "click chemistry", thereby offering a wide range of preparative and analytical options...
March 6, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28260496/biomedical-applications-of-multifunctional-gold-based-nanocomposites
#19
REVIEW
L A Dykman, N G Khlebtsov
Active application of gold nanoparticles for various diagnostic and therapeutic purposes started in recent decades due to the emergence of new data on their unique optical and physicochemical properties. In addition to colloidal gold conjugates, growth in the number of publications devoted to the synthesis and application of multifunctional nanocomposites has occurred in recent years. This review considers the application in biomedicine of multifunctional nanoparticles that can be produced in three different ways...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28258313/catechol-glucosides-act-as-donor-acceptor-substrates-of-glucansucrase-enzymes-of-lactobacillus-reuteri
#20
Evelien M Te Poele, Vincent Valk, Tim Devlamynck, Sander S van Leeuwen, Lubbert Dijkhuizen
Previously, we have shown that the glucansucrase GtfA-ΔN enzyme of Lactobacillus reuteri 121, incubated with sucrose, efficiently glucosylated catechol and we structurally characterized catechol glucosides with up to five glucosyl units attached (te Poele et al. in Bioconjug Chem 27:937-946, 2016). In the present study, we observed that upon prolonged incubation of GtfA-ΔN with 50 mM catechol and 1000 mM sucrose, all catechol had become completely glucosylated and then started to reappear. Following depletion of sucrose, this glucansucrase GtfA-ΔN used both α-D-Glcp-catechol and α-D-Glcp-(1→4)-α-D-Glcp-catechol as donor substrates and transferred a glucose unit to other catechol glycoside molecules or to sugar oligomers...
March 3, 2017: Applied Microbiology and Biotechnology
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