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Bioconjugate Chemistry

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https://www.readbyqxmd.com/read/28548819/tuning-the-properties-of-polymer-capsules-for-cellular-interactions
#1
Huanli Sun, Jiwei Cui, Yi Ju, Xi Chen, Edgar H H Wong, Jenny Tran, Greg G Qiao, Frank Caruso
Particle-cell interactions are governed by, among other factors, the composition and surface properties of the particles. Herein, we report the preparation of various polymer capsules with different compositions and properties via atom transfer radical polymerization mediated continuous assembly of polymers (CAPATRP), where the cellular interactions of these capsules, particularly fouling and specific targeting, are examined by flow cytometry and deconvolution microscopy. Acrylated eight-arm poly(ethylene glycol) (8-PEG) and poly(N-(2-hydroxypropyl)-methacrylamide) (PHPMA) as well as methacrylated hyaluronic acid (HA), poly(glutamic acid) (PGA), and poly(methacrylic acid) (PMA) are used as macro-cross-linkers to obtain a range of polymer capsules with different compositions (PEG, PHPMA, HA, PGA, and PMA)...
May 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28489355/conjugate-of-an-igg-binding-domain-with-botulinum-neurotoxin-a-lacking-the-acceptor-moiety-targets-its-snare-protease-into-trka-expressing-cells-when-coupled-to-anti-trka-igg-or-fc-%C3%AE-ngf
#2
Marc Nugent, Jiafu Wang, Gary Lawrence, Tomas Zurawski, Joan A Geoghegan, J Oliver Dolly
Numerous naturally occurring toxins can perturb biological systems when they invade susceptible cells. Coupling of pertinent targeting ligands to the active domains of such proteins provides a strategy for directing these to particular cellular populations implicated in disease. A novel approach described herein involved fusion of one mutated immunoglobulin G (IgG) binding moiety of staphylococcal protein A to the SNARE protease and translocation domain of botulinum neurotoxin A (BoNT/A). This chimera could be monovalently coupled to IgG or via its Fc region to recombinant targeting ligands...
May 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28525708/affinity-based-assembly-of-peptides-on-plasmonic-nanoparticles-delivered-intracellularly-with-light-activated-control
#3
Demosthenes P Morales, William Wonderly, Xiao Huang, Meghan McAdams, Amanda Chron, Norbert O Reich
We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and internalization peptide attachment are an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol labeled scaffolds terminated with the affinity partner...
May 19, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28520406/characterization-of-dspe-peg2000-and-its-complex-with-doxorubicin-using-nmr-spectroscopy-and-molecular-dynamics
#4
Weidong Hu, Allen Mao, Patty Wong, Adrien Larsen, Paul J Yazaki, Jeffrey Y C Wong, John E Shively
Polyethyleneglycol (PEG) lipid nanoparticles (LNPs) spontaneously assemble in water forming uniform sized nanoparticles incorporating drugs with prolonged blood clearance over drugs alone. Previously, DSPE-PEG2000 and several drug adducts, including doxorubicin, were analyzed by a combination of physical and molecular dynamic (MD) studies. In this study a complete chemical shift assignment of DSPE-PEG2000 plus or minus doxorubicin was achieved using NMR 1D-selNOESY, NOESY, COSY, TOCSY, HSQC and HSQC-TOCSY. Chemical shift perturbation, titration, relaxation enhancement and NOESY analysis combined with MD reveal detailed structural information at the atomic level including location of doxorubicin in the micelle, its binding constant, the hydrophilic shell organization and the mobility of PEG2000 tail, demonstrating NMR spectroscopy can characterize drug-DSPE-PEG2000 micelles with molecular weights above 180kDa...
May 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28514139/bioorthogonal-protein-conjugation-application-to-the-development-of-a-highly-sensitive-bioluminescent-immunoassay-for-the-detection-of-interferon-%C3%AE
#5
Angeliki Moutsiopoulou, Eric A Hunt, David Broyles, Christie Ataides Pereira, Kristen Woodward, Emre Dikici, Angel E Kaifer, Sylvia Daunert, Sapna Deo
Bioorthogonal conjugation eliminates the shortcomings of classical conjugation methods. The conjugation of antibodies to reporter proteins, such as bioluminescent protein, can be controlled with orthogonal conjugation methods. Here we report a bioluminescent immunoassay for the sensitive detection of interferon-γ (IFN-γ) that utilizes orthogonal conjugation of bioluminescent protein, Gaussia luciferase to anti-IFN-γ antibody. The IFN-γ is produced by the immune system and the detection of the IFN-γ is pivotal for the detection of persistent viral and bacterial infections...
May 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28510418/conjugation-reaction-with-8-arm-peg-markedly-improves-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#6
Xiaowei Sun, Weili Yu, Quanhai Pang, Tao Hu
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. CFP10 and TB10.4 are two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen...
May 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28505420/immobilization-of-l-asparaginase-on-carrier-materials-a-comprehensive-review
#7
Ahmet Ulu, Burhan Ates
There are two major applications of L-asparaginase (L-ASNase): Cancer therapy and food industry. Especially, its chemotherapeutic effect has attracted interest of the scientific community and of individual scientists. Therefore, to protect the intrinsic activity and half-time of L-ASNase, several carriers and immobilization techniques for immobilization of L-ASNase have been described in articles. Unfortunately, a comprehensive review about immobilization of L-ASNase wasn't written until now. In this review, we lengthily discussed the carriers for L-ASNase by illustrating immobilization findings including both past and present applications...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28504875/selection-of-natural-peptide-ligands-for-copper-catalyzed-azide-alkyne-cycloaddition-catalysis
#8
Allison G Aioub, Lindsay Dahora, Kelly Gamble, M G Finn
The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful tool for making connections in both organic reactions and biological systems. However, the use of this ligation process in living cells is limited by the toxicity associated with unbound copper ions. As an initial attempt to create peptide-based accelerating ligands capable of cellular expression, we performed synthesis and selection for such species on solid-phase synthesis beads bearing both candidate ligand and alkyne substrate...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28485576/new-lanthanide-tag-for-the-generation-of-pseudocontact-shifts-in-dna-by-site-specific-ligation-to-a-phosphorothioate-group
#9
Zuyan Wu, Michael D Lee, Thomas J Carruthers, Monika Szabo, Matthew L Dennis, James D Swarbrick, Bim Graham, Gottfried Otting
Pseudocontact shifts (PCS) generated by paramagnetic lanthanides provide a rich source of long-range structural restraints that can readily be measured by nuclear magnetic resonance (NMR) spectroscopy. Many different lanthanide-binding tags have been designed for site-specific tagging of proteins, but established routes for tagging DNA with a single metal ion rely on difficult chemical synthesis. Here we present a simple and practical strategy for site-specific tagging of inexpensive phosphorothioate (PT) oligonucleotides...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28482158/magnetically-guided-viral-transduction-of-gene-based-sensitization-for-localized-photodynamic-therapy-to-overcome-multidrug-resistance-in-breast-cancer-cells
#10
Zi-Xian Liao, Ivan M Kempson, Yu-Chen Fa, Meng-Chia Liu, Li-Chen Hsieh, Kuo-Yen Huang, Li-Feng Wang
Chemotherapy represents a conventional treatment for many cancers at different stages and is either solely prescribed or concomitant to surgery, radiotherapy, or both. However, treatment is tempered in instances of acquired drug resistance in response to either chemotherapy or targeted therapy, leading to therapeutic failure. To overcome this challenge, many studies focus on how cancer cells manipulate their genomes and metabolism to prevent drug influx and facilitate the efflux of accumulated chemotherapy drugs...
May 15, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28485976/use-of-nanoparticle-contrast-agents-for-cell-tracking-with-computed-tomography
#11
Johoon Kim, Peter Chhour, Jessica Hsu, Harold I Litt, Victor A Ferrari, Rachela Popovtzer, David P Cormode
Efforts to develop novel cell-based therapies originated with the first bone marrow transplant on a leukemia patient in 1956. Preclinical and clinical examples of cell-based treatment strategies have shown promising results across many disciplines in medicine, with recent advances in immune cell therapies for cancer producing remarkable response rates, even in patients with multiple treatment failures. However, cell-based therapies suffer from inconsistent outcomes, motivating the search for tools that allow monitoring cell delivery and behavior in vivo...
May 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28485595/polymer-klak-peptide-conjugates-induce-cancer-cell-death-through-synergistic-effects-of-mitochondria-damage-and-autophagy-blockage
#12
Zeng-Ying Qiao, Wen-Jia Lai, Yao-Xin Lin, Dan Li, Xiaohui Nan, Yi Wang, Hao Wang, Qiaojun Fang
Nanoscaled polymer-peptide conjugates (PPCs) containing both functional peptides and synthetic polymer comprise a new family of biomaterials that can circumvent the limitation of peptides alone. Our previous work showed that PPCs with the therapeutic peptide KLAK, especially PPCs with shorter PEG spacers and a higher degree of polymerization, exhibit enhanced antitumor effects through disrupting mitochondrial membranes. However, as PPCs have a spherical nanostructure (45~60 nm), this may have other effects besides the conjugated therapeutic peptide KLAK itself when they enter cancer cells...
May 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28437092/facile-quenching-and-spatial-patterning-of-cylooctynes-via-strain-promoted-alkyne-azide-cycloaddition-of-inorganic-azides
#13
Matthew Bjerknes, Hazel Cheng, Christopher D McNitt, Vladimir V Popik
Little is known about the reactivity of strain-promoted alkyne-azide cycloaddition (SPAAC) reagents with inorganic azides. We explore the reactions of a variety of popular SPAAC reagents with sodium azide and hydrozoic acid. We find that the reactions proceed in water at rates comparable to those with organic azides, yielding in all cases a triazole adduct. The azide ion's utility as a cyclooctyne quenching reagent is demonstrated by using it to spatially pattern uniformly doped hydrogels. The facile quenching of cyclooctynes demonstrated here should be useful in other bioorthogonal ligation techniques in which cyclooctynes are employed, including SPANC, Diels-Alder, and thiol-yne...
May 9, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28482148/bacteriophages-as-factories-for-eu2o3-nanoparticle-synthesis
#14
Piotr Golec, Kamila Żelechowska, Joanna Karczewska-Golec, Jakub Karczewski, Adam Lesniewski, Marcin Łoś, Grzegorz Wegrzyn, Andrzej M Klonkowski
The use of phage display to identify peptides with an ability to bind Eu2O3 is demonstrated in this report. This is the first report of modified phages specifically binding a lanthanide. The peptides exposed on virions revealed very strong binding to Eu2O3 nanoparticles and the ability to catalyze Eu2O3 nanoparticles' formation from Eu(OH)3 and Eu(NO3)3 solutions. The luminescence emission spectrum of Eu3+ ions indicated that these ions existed mostly in sites deviated from the inversion symmetry in crystalline Eu2O3 aggregates and gelatinous Eu(OH)3 precipitate...
May 8, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28475311/targeting-and-internalization-of-liposomes-by-bladder-tumor-cells-using-a-fibronectin-attachment-protein-derived-peptide-lipopolymer-conjugate
#15
Young Lee, Erin Kischuk, Scott Crist, Timothy L Ratliff, David H Thompson
A synthetic peptidolipopolymer conjugate, incorporated into liposomes to promote specific binding to the fibronectin (FBN) matrix surrounding bladder tumor cells and promote cellular internalization of FBN-integrin complexes, is reported. The peptide promotes association with MB49 mouse model bladder tumor cells in a sequence-specific and concentration-dependent manner, with the maximum cell association occurring at 2 mol % RWFV-PEG2000-DSPE. Double PEGylation of the liposome membrane (i.e., 4 mol % mPEG1000-DSPE + 2 mol % RWFV-PEG2000-DSPE) enhanced binding by >1...
May 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28441501/hooked-on-cryogels-a-carbamate-linker-based-depot-for-slow-drug-release
#16
Duygu Aydin, Mehmet Arslan, Amitav Sanyal, Rana Sanyal
Poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels containing activated carbonate groups as amine reactive handles to facilitate drug conjugations through carbamate linkages were fabricated and evaluated as slow releasing drug reservoirs. As an initial approach, photopolymerization of N-hydroxysuccinimide (NHS)-activated carbonate functional group containing monomer and PEG-methacrylate in the presence of a cross-linker was utilized to obtain bulk hydrogels with high gel conversions. The resultant hydrogels possessed moderate water uptake (170-340%) which was dependent on the monomer ratios...
May 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28441015/-bottom-up-construction-of-multi-polyprodrug-arm-hyperbranched-amphiphiles-for-cancer-therapy
#17
Pei Sun, Dong Chen, Hongping Deng, Nan Wang, Ping Huang, Xin Jin, Xinyuan Zhu
Despite the great advantages of polymer-drug conjugates (PDC) in cancer therapy, control of the drug loading site and degree via a facile approach remains a great challenge. Herein, by combining the controllability of the "bottom-up" strategy and the stability of multiarm hyperbranched amphiphiles, we have developed novel multi-polyprodrug-arm hyperbranched amphiphiles (H40-star-(PHCPTMA-b-PMPC), hPCM) via reversible addition-fragmentation chain transfer (RAFT) polymerization for cancer therapy. The hPCM was constructed via two-step polymerization of an acid-labile prodrug monomer and a zwitterionic monomer, respectively...
May 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28437083/dual-plug-and-display-synthetic-assembly-using-orthogonal-reactive-proteins-for-twin-antigen-immunization
#18
Karl D Brune, Can M Buldun, Yuanyuan Li, Iona J Taylor, Florian Brod, Sumi Biswas, Mark Howarth
Engineering modular platforms to control biomolecular architecture can advance both the understanding and the manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle and to induce broader immunity protective across strains or even against distinct diseases. Here, we design a dually addressable synthetic nanoparticle by engineering the multimerizing coiled-coil IMX313 and two orthogonally reactive split proteins...
May 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28316241/investigating-the-cellular-specificity-in-tumors-of-a-surface-converting-nanoparticle-by-multimodal-imaging
#19
Francois Fay, Line Hansen, Stefanie J C G Hectors, Brenda L Sanchez-Gaytan, Yiming Zhao, Jun Tang, Jazz Munitz, Amr Alaarg, Mounia S Braza, Anita Gianella, Stuart A Aaronson, Thomas Reiner, Jørgen Kjems, Robert Langer, Freek J M Hoeben, Henk M Janssen, Claudia Calcagno, Gustav J Strijkers, Zahi A Fayad, Carlos Pérez-Medina, Willem J M Mulder
Active targeting of nanoparticles through surface functionalization is a common strategy to enhance tumor delivery specificity. However, active targeting strategies tend to work against long polyethylene glycol's shielding effectiveness and associated favorable pharmacokinetics. To overcome these limitations, we developed a matrix metalloproteinase-2 sensitive surface-converting polyethylene glycol coating. This coating prevents nanoparticle-cell interaction in the bloodstream, but, once exposed to matrix metalloproteinase-2, i...
May 5, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28471638/harnessing-supramolecular-and-peptidic-self-assembly-for-the-construction-of-reinforced-polymeric-tissue-scaffolds
#20
Chase B Thompson, LaShanda T J Korley
The repair and regeneration of the body's tissue using polymeric materials remains a main focus of biomaterials research. While hydrogels and elastomers have shown biocompatibility and high extensibility, they lack the required toughness to host proliferating cells. As the need for robust polymeric scaffolds grows, new technologies must emerge to meet the stringent physical and biological needs of proliferating cells. To this end, the utilization of self-assembling motifs allows for the construction of versatile networks in which cells can grow...
May 4, 2017: Bioconjugate Chemistry
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