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    5284 results match your criteria Bioconjugate Chemistry [Journal]

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    Polymer Conjugation to Enhance Cellulase Activity and Preserve Thermal and Functional Stability.
    Bioconjug Chem 2017 Sep 21. Epub 2017 Sep 21.
    A thermophilic cellulase, FnCel5a, from Fervidobacterium nodosum was conjugated with various functional polymers including cationic, anionic, and strongly and weakly hydrogen bonding polymers. The activity of FnCel5a toward a high molecular weight carboxymethyl cellulose substrate was enhanced by polymer conjugation. Activity enhancements of 50% or greater observed for acrylamide and mixed N,N-dimethyl acrylamide/2-(N,N-dimethylamino)ethyl methacrylate polymers suggesting that the greatest enhancements were caused by polymers capable of non-covalent interactions with the substrate. Read More

    Avidin/biotin bioinspired platform for dual in vivo 18F-PET/NIRF molecular imaging.
    Bioconjug Chem 2017 Sep 20. Epub 2017 Sep 20.
    The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of innovative multimodal PET/NIRF probes a very exciting prospect. Herein, the bioinspired design of novel platform exploiting the strength and specificity of interactions between radioactive and fluorescent biotin derivatives and an avidin core is reported. The combination of an original [18F]fluoropyridinylated-biotin derivative and commercially available fluorescent biotin derivatives (Atto-425® and Atto-680®) is investigated. Read More

    Hydrogel Tethering Enhances Interdomain Stabilization of Single Chain Antibodies.
    Bioconjug Chem 2017 Sep 20. Epub 2017 Sep 20.
    Here we identify the importance of molecular crowding agents in the functional stabilization of scFv antibodies. Antibodies were tethered through an engineered calmodulin (CaM) binding peptide into a stimulus-responsive hydrogel composed of poly-(ethylene glycol) (PEG) functionalized CaM. Macromolecular crowding is modulated by transient heating, which acts to decrease effective pore sizes. Read More

    Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs.
    Bioconjug Chem 2017 Sep 22. Epub 2017 Sep 22.
    Department of Chemistry, College of Chemistry and Chemical Engineering, State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Xiamen University , Xiamen, 361005, P.R. China.
    Targeted prodrugs exploiting cleavable linkers capable of responding to endogenous stimuli have increasingly been explored for cancer therapy. Successful application of these prodrug designs relies on the manipulation of both stability and responsiveness of the cleavable linkers, which, however, are difficult to be finely regulated, particularly for acid-responsive acylhydrazone bonds. Here we developed a new class of peptide-bridged twin-acylhydrazone linkers (PTA linkers) displaying both an ultrahigh stability and a rapid responsiveness-highly stable in neutral and acidic conditions due to the effect of cooperativity between the two acylhydrazone bonds, easily cleavable in acidic conditions after enzymatically triggered unlocking of the two bonds. Read More

    Automated solid phase click synthesis of oligonucleotide conjugates: from small molecules to diverse N-acetylgalactosamine clusters.
    Bioconjug Chem 2017 Sep 18. Epub 2017 Sep 18.
    We developed a novel technique for efficient conjugation of oligonucleotides with various alkyl azides (fluorescent dyes, biotin, cholesterol, GalNAc, etc.) using CuAAC on solid phase and CuI·P(OEt)3 as a catalyst. Conjugation is carried out in an oligonucleotide synthesizer in fully automated mode and is coupled to oligonucleotide synthesis and on-column deprotection. Read More

    Tumor Cell-Specific Nuclear Targeting of Functionalized Graphene Quantum Dots In Vivo.
    Bioconjug Chem 2017 Sep 13. Epub 2017 Sep 13.
    Specific targeting of tumor tissues is essential for tumor imaging and therapeutics but remains challenging. Here, we report an unprecedented method using synthetic sulfonic-graphene quantum dots (sulfonic-GQDs) to exactly target the cancer cell nuclei in vivo without any bio- ligand modification, with no intervention in cells of normal tissues. The key factor for such selectivity is the high interstitial fluid pressure (IFP) in tumor tissues, which allows the penetration of sulfonic-GQDs into the plasma membrane of tumor cells. Read More

    Synthesis, Radiolabeling, and Characterization of Plasma Protein-Binding Ligands: Potential Tools for Modulation of the Pharmacokinetic Properties of (Radio)Pharmaceuticals.
    Bioconjug Chem 2017 Sep 12;28(9):2372-2383. Epub 2017 Sep 12.
    Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut , 5232 Villigen-PSI, Switzerland.
    The development of (radio)pharmaceuticals with favorable pharmacokinetic profiles is crucial for allowing the optimization of the imaging or therapeutic potential and the minimization of undesired side effects. The aim of this study was, therefore, to evaluate and compare three different plasma protein binders (PPB-01, PPB-02, and PPB-03) that are potentially useful in combination with (radio)pharmaceuticals to enhance their half-life in the blood. The entities were functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator via a l-lysine and β-alanine linker moiety using solid-phase peptide chemistry and labeled with (177)Lu (T1/2 = 6. Read More

    Transglutaminase-Catalyzed Bioconjugation Using One-Pot Metal-Free Bioorthogonal Chemistry.
    Bioconjug Chem 2017 Sep 14. Epub 2017 Sep 14.
    PROTEO, Québec Network for Protein Function, Engineering and Applications , Québec, G1V 0A6, Canada.
    General approaches for controlled protein modification are increasingly sought-after in the arena of chemical biology. Here, using bioorthogonal reactions, we present combinatorial chemoenzymatic strategies to effectuate protein labeling. A total of three metal-free conjugations were simultaneously or sequentially incorporated in a one-pot format with microbial transglutaminase (MTG) to effectuate protein labeling. Read More

    Recent Developments in Antimicrobial Peptide Conjugated Gold Nanoparticles.
    Bioconjug Chem 2017 Sep 11. Epub 2017 Sep 11.
    The escalation of multidrug-resistant pathogens has created a dire need to develop novel ways of addressing this global therapeutic challenge. Because of their antimicrobial activities, combination of antimicrobial peptides (AMPs) and nanoparticles is a promising tool to kill drug resistant pathogens. In recent years, several studies using AMP-nanoparticle conjugates, especially metallic nanoparticles, as potential antimicrobial agents against drug resistant pathogens have been published. Read More

    Bioconjugation Approaches to Producing Subunit Vaccines Composed of Protein or Peptide Antigens and Covalently Attached Toll-Like Receptor Ligands.
    Bioconjug Chem 2017 Sep 22. Epub 2017 Sep 22.
    School of Pharmacy, The University of Queensland , Woolloongabba 4102, Queensland, Australia.
    Traditional vaccines derived from attenuated or inactivated pathogens are effective at inducing antibody-based protective immune responses but tend to be highly reactogenic, causing notable adverse effects. Vaccines with superior safety profiles can be produced by subunit approaches, utilizing molecularly defined antigens (e.g. Read More

    Attachment Site Cysteine Thiol pKa Is a Key Driver for Site-Dependent Stability of THIOMAB Antibody-Drug Conjugates.
    Bioconjug Chem 2017 Sep 22. Epub 2017 Sep 22.
    Genentech Incorporated , 1 DNA Way, South San Francisco, California 94080, United States.
    The incorporation of cysteines into antibodies by mutagenesis allows for the direct conjugation of small molecules to specific sites on the antibody via disulfide bonds. The stability of the disulfide bond linkage between the small molecule and the antibody is highly dependent on the location of the engineered cysteine in either the heavy chain (HC) or the light chain (LC) of the antibody. Here, we explore the basis for this site-dependent stability. Read More

    Peptide dendrons as thermal stability amplifiers for IgG1 monoclonal antibody biotherapeutics.
    Bioconjug Chem 2017 Sep 7. Epub 2017 Sep 7.
    Biotherapeutics such as monoclonal antibodies (mAbs) have a major share of the pharmaceutical industry for treatment of life-threatening chronic diseases such as cancer, skin ailments and immune disorders. Instabilities such as aggregation, fragmentation, oxidation and reduction have resulted in the practice of storing these products at low temperatures (-80ºC to -20ºC). However, reliable storage at these temperatures can be a challenge, particularly in developing and underdeveloped countries and hence lately there has been a renewed interest in creating formulations that would offer stability at higher temperatures (25ºC to 55ºC). Read More

    Amino acid functionalised inorganic nanoparticles as cutting-edge therapeutic and diagnostic agents.
    Bioconjug Chem 2017 Sep 6. Epub 2017 Sep 6.
    The field of medical diagnostics and therapeutics is being revolutionized by nanotechnology, from targeted drug delivery to cancer immunotherapy. Inorganic nanoparticles are widely used, albeit problems with agglutination, cytotoxicity, free radical generation and instability in some biological environments, limits their utility. Conjugation of biomolecules such as peptides to the surface of nanoparticles can mitigate such problems, as well as confer specialized theranostic (therapeutic and/or diagnostic) properties, useful across biomedical applications such as vaccines, drug delivery and in vivo imaging. Read More

    Selective and Cleavable Extraction of Sialo-glycoproteins by Disulfide-Linked Amino-oxy-Functionalized Fe3O4 Magnetic Nanoparticles.
    Bioconjug Chem 2017 Sep 13. Epub 2017 Sep 13.
    Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education of China, College of Chemistry and Chemical Engineering, Hunan Normal University , No. 36, Lushan Road, Changsha, China 410081.
    The low abundance of sialo-glycoprotein hampered the separation, enrichment, and analysis of sialo-glycoproteins, which are critical for studying their functions. Here, we designed cleavable amino-oxy functionalized magnetic materials and employed to fast and selective isolate sialo-glycoproteins. This includes the ligation of disulfide-linked amino-oxy-functionalized magnetic nanoparticles with periodate-treated glycoproteins or cells, followed by magnetic separation. Read More

    Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by Ca(2+) Sensitizers and a Ca(2+) Sensitivity Blunting Phosphomimic, cTnT(T204E).
    Bioconjug Chem 2017 Sep 18. Epub 2017 Sep 18.
    The Voiland School of Chemical Engineering and Bioengineering and ‡The Department of Integrated Neuroscience and Physiology, Washington State University , Pullman, Washington 99164, United States.
    Several studies have suggested that conformational dynamics are important in the regulation of thin filament activation in cardiac troponin C (cTnC); however, little direct evidence has been offered to support these claims. In this study, a dye homodimerization approach is developed and implemented that allows the determination of the dynamic equilibrium between open and closed conformations in cTnC's hydrophobic cleft. Modulation of this equilibrium by Ca(2+), cardiac troponin I (cTnI), cardiac troponin T (cTnT), Ca(2+)-sensitizers, and a Ca(2+)-desensitizing phosphomimic of cTnT (cTnT(T204E) is characterized. Read More

    Erythrocyte Membrane-Wrapped pH Sensitive Polymeric Nanoparticles for Non-Small Cell Lung Cancer Therapy.
    Bioconjug Chem 2017 Sep 14. Epub 2017 Sep 14.
    Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai 200062, P.R. China.
    The application of nano drug delivery systems (NDDSs) may enhance the effectiveness of chemotherapeutic drugs in vivo. However, the short blood circulation time and poor drug release profile in vivo are still two problems with them. Herein, by using red blood cell membrane (RBCm) wrapping and pH sensitive technology, we prepared RBCm wrapped pH sensitive poly(l-γ-glutamylcarbocistein)-paclitaxel (PGSC-PTX) nanoparticles (PGSC-PTX@RBCm NPs), to prolong the circulation time in blood and release PTX timely and adequately in acidic tumor environment. Read More

    Generation of Clickable Pittsburgh Compound B for the Detection and Capture of β-Amyloid in Alzheimer's Disease Brain.
    Bioconjug Chem 2017 Sep 22. Epub 2017 Sep 22.
    Department of Biochemistry, ‡Yerkes National Primate Research Center, §Department of Pathology and Laboratory Medicine, and ∥Department of Neurology, Emory University , Atlanta, Georgia 30322, United States.
    The benzothiazole-aniline derivative Pittsburgh Compound B (PiB) is the prototypical amyloid affinity probe developed for the in vivo positron emission tomography (PET) detection of amyloid beta (Aβ) deposits in Alzheimer's disease (AD). Specific high-affinity binding sites for PiB have been found to vary among AD cases with comparable Aβ load, and they are virtually absent on human-sequence Aβ deposits in animal models, none of which develop the full phenotype of AD. PiB thus could be an informative probe for studying the pathobiology of Aβ, but little is known about the localization of PiB binding at the molecular or structural level. Read More

    Enhanced Photobactericidal and Targeting Properties of a Cationic Porphyrin following the Attachment of Polymyxin B.
    Bioconjug Chem 2017 Sep 11;28(9):2493-2506. Epub 2017 Sep 11.
    Université de Limoges, Laboratoire de Chimie des Substances Naturelles , EA 1069, 123 Avenue Albert Thomas, 87060 Limoges, CEDEX, France.
    A novel compound consisting of a cationic porphyrin covalently attached to a derivative of polymyxin B has been synthesized and presents enhanced activity and targeting properties compared to the usual cationic porphyrins recognized as efficient photosensitizers in photodynamic antimicrobial chemotherapy (PACT). A synthesis pathway was established to preserve the bactericidal activity of the peptide. Accordingly, the N-terminal amino acid (l-2,4-diaminobutyric acid) of polymyxin B (PMB) was switched for a cysteine residue. Read More

    Affinity-Based Purification of Polyisocyanopeptide Bioconjugates.
    Bioconjug Chem 2017 Sep 15. Epub 2017 Sep 15.
    Department of Molecular Materials, Institute for Molecules and Materials, Radboud University , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
    Water-soluble polyisocyanopeptides (PICs) are a new class of synthetic polymers that mimic natural protein-based filaments. Their unique semiflexible properties combined with a length of several hundred nanometers have recently enabled a number of biomedical applications ranging from tissue engineering to cancer immunotherapy. One crucial step toward the further development of PICs for these applications is the efficient and controlled synthesis and purification of PIC-biomolecule conjugates. Read More

    Diels-Alder "Clickable" Biodegradable Nanofibers: Benign Tailoring of Scaffolds for Biomolecular Immobilization and Cell Growth.
    Bioconjug Chem 2017 Sep 5;28(9):2420-2428. Epub 2017 Sep 5.
    Department of Chemistry and ‡Center for Life Sciences and Technologies, Bogazici University , Bebek 34342, Istanbul, Turkey.
    Biodegradable polymeric nanofibers have emerged as promising candidates for several biomedical applications such as tissue engineering and regenerative medicine. Many of these applications require modification of these nanofibers with small ligands or biomolecules such as peptides and other growth factors, which necessitates functionalization of these materials in mild and benign fashion. This study reports the design, synthesis, and functionalization of such nanofibers and evaluates their application as a cell culture scaffold. Read More

    DNA-Compatible Nitro Reduction and Synthesis of Benzimidazoles.
    Bioconjug Chem 2017 Sep 13. Epub 2017 Sep 13.
    Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine , Houston, Texas 77030, United States.
    DNA-encoded chemical libraries have emerged as a cost-effective alternative to high-throughput screening (HTS) for hit identification in drug discovery. A key factor for productive DNA-encoded libraries is the chemical diversity of the small molecule moiety attached to an encoding DNA oligomer. The library structure diversity is often limited to DNA-compatible chemical reactions in aqueous media. Read More

    Intracellular Assembly of Nuclear-Targeted Gold Nanosphere Enables Selective Plasmonic Photothermal Therapy of Cancer by Shifting Their Absorption Wavelength toward Near-Infrared Region.
    Bioconjug Chem 2017 Sep 7;28(9):2452-2460. Epub 2017 Sep 7.
    Laser Dynamics Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332, United States.
    Despite the important applications of near-infrared (NIR) absorbing nanomaterials in plasmonic photothermal therapy (PPT), their high yield synthesis and nonspecific heating during the active- and passive-targeted cancer therapeutic strategies remain challenging. In the present work, we systematically demonstrate that in situ aggregation of typical non-NIR absorbing plasmonic nanoparticles at the nuclear region of the cells could translate them into an effective NIR photoabsorber in plasmonic photothermal therapy of cancer due to a significant shift of the plasmonic absorption band to the NIR region. We evaluated the potential of nuclear-targeted AuNSs as photoabsorber at various stages of endocytosis by virtue of their inherent in situ assembling capabilities at the nuclear region of the cells, which has been considered as one of the most thermolabile structures within the cells, to selectively destruct cancer cells with minimal damage to healthy cells. Read More

    Detection of Alkynes via Click Chemistry with a Brominated Coumarin Azide by Simultaneous Fluorescence and Isotopic Signatures in Mass Spectrometry.
    Bioconjug Chem 2017 Sep 11;28(9):2302-2309. Epub 2017 Sep 11.
    Barnett Institute of Chemical and Biological Analysis, Department of Chemistry and Chemical Biology, Northeastern University , 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
    Alkynes are a key component of click chemistry and used for a wide variety of applications including bioconjugation, selective tagging of protein modifications, and labeling of metabolites and drug targets. However, challenges still exist for detecting alkynes because most 1,2,3-triazole products from alkynes and azides do not possess distinct intrinsic properties that can be used for their facile detection by either fluorescence or mass spectrometry. To address this critical need, a novel brominated coumarin azide was used to tag alkynes and detect alkyne-conjugated biomolecules. Read More

    Nanofitin as a New Molecular-Imaging Agent for the Diagnosis of Epidermal Growth Factor Receptor Over-Expressing Tumors.
    Bioconjug Chem 2017 Sep 12;28(9):2361-2371. Epub 2017 Sep 12.
    Affilogic SAS , 21 rue La Noue Bras de Fer, 44200 Nantes, France.
    Epidermal growth-factor receptor (EGFR) is involved in cell growth and proliferation and is over-expressed in malignant tissues. Although anti-EGFR-based immunotherapy became a standard of care for patients with EGFR-positive tumors, this strategy of addressing cancer tumors by targeting EGFR with monoclonal antibodies is less-developed for patient diagnostic and monitoring. Indeed, antibodies exhibit a slow blood clearance, which is detrimental for positron emission tomography (PET) imaging. Read More

    Site-Specific Conjugation to Native and Engineered Lysines in Human Immunoglobulins by Microbial Transglutaminase.
    Bioconjug Chem 2017 Sep 6;28(9):2471-2484. Epub 2017 Sep 6.
    Morphotek Inc. , 210 Welsh Pool Road, Exton, Pennsylvania 19341, United States.
    The use of microbial transglutaminase (MTG) to produce site-specific antibody-drug conjugates (ADCs) has thus far focused on the transamidation of engineered acyl donor glutamine residues in an antibody based on the hypothesis that the lower specificity of MTG for acyl acceptor lysines may result in the transamidation of multiple native lysine residues, thereby yielding heterogeneous products. We investigated the utilization of native IgG lysines as acyl acceptor sites for glutamine-based acyl donor substrates. Of the approximately 80 lysines in multiple recombinant IgG monoclonal antibodies (mAbs), none were transamidated. Read More

    Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins.
    Bioconjug Chem 2017 Sep 6;28(9):2440-2451. Epub 2017 Sep 6.
    Biomaterials and Polymer Science, Department of Bio- and Chemical Engineering, TU Dortmund , Emil-Figge-Straße 66, 44227 Dortmund, Germany.
    The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. Read More

    Doxorubicin and Indocyanine Green Loaded Hybrid Bicelles for Fluorescence Imaging Guided Synergetic Chemo/Photothermal Therapy.
    Bioconjug Chem 2017 Sep 24;28(9):2410-2419. Epub 2017 Aug 24.
    Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
    Hybrid bicelles have been demonstrated to have great potential for hydrophobic drug delivery. Herein, we report a near-infrared light-driven, temperature-sensitive hybrid bicelles co-encapsulating hydrophobic doxorubicin (DOX) and indocyanine green (ICG) (DOX/ICG@HBs). Encapsulation of ICG into the lipid bilayer membrane of DOX/ICG@HBs results in higher photostability than free ICG. Read More

    Dynamic Covalent Hydrogels for Triggered Cell Capture and Release.
    Bioconjug Chem 2017 Sep 22;28(9):2235-2240. Epub 2017 Aug 22.
    School of Chemical and Biomedical Engineering, Particulate Fluids Processing Centre and ‡Polymer Science Group, Department of Chemical and Biomolecular Engineering, Particulate Fluids Processing Centre, University of Melbourne , Parkville, Melbourne, Victoria 3010, Australia.
    A dual-responsive, cell capture and release surface was prepared through the incorporation of phenylboronic acid (PBA) groups into an oxime-based polyethylene glycol (PEG) hydrogel. Owing to its PEG-like properties, the unfunctionalized hydrogel was nonfouling. The use of highly efficient oxime chemistry allows the incorporation of commercially available 3,5-diformylphenyl boronic acid into the hydrogel matrix. Read More

    Assembling Glycan-Charged Dolichol Phosphates: Chemoenzymatic Synthesis of a Haloferax volcanii N-Glycosylation Pathway Intermediate.
    Bioconjug Chem 2017 Sep 30;28(9):2461-2470. Epub 2017 Aug 30.
    Department of Life Sciences, Ben Gurion University of the Negev , Beersheva 8410501, Israel.
    N-glycosylation, the covalent attachment of glycans to select protein target Asn residues, is a post-translational modification performed by all three domains of life. In the halophilic archaea Haloferax volcanii, in which understanding of this universal protein-processing event is relatively well-advanced, genes encoding the components of the archaeal glycosylation (Agl) pathway responsible for the assembly and attachment of an N-linked pentasaccharide have been identified. As elsewhere, the N-linked glycan is assembled on phosphodolichol carriers before transfer to target Asn residues. Read More

    Synthesis, Characterization, and Selective Delivery of DARPin-Gold Nanoparticle Conjugates to Cancer Cells.
    Bioconjug Chem 2017 Aug 22. Epub 2017 Aug 22.
    Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences and the Center of Nanoscience and Nanotechnology, Tel Aviv University , Ramat Aviv, Tel Aviv 69978, Israel.
    We demonstrate that the designed ankyrin repeat protein (DARPin)_9-29, which specifically targets human epidermal growth factor receptor 2 (HER 2), binds tightly to gold nanoparticles (GNPs). Binding of the protein strongly increases the colloidal stability of the particles. The results of experimental analysis and molecular dynamics simulations show that approximately 35 DARPin_9-29 molecules are bound to the surface of a 5 nm GNP and that the binding does not involve the receptor-binding domain of the protein. Read More

    Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations.
    Bioconjug Chem 2017 Sep 29;28(9):2327-2339. Epub 2017 Aug 29.
    Department of Physics and ‡Department of Chemistry, Nanoscience Center, University of Jyväskylä , Jyväskylä, Finland FI-40014.
    Biocompatible gold nanoclusters can be utilized as contrast agents in virus imaging. The labeling of viruses can be achieved noncovalently but site-specifically by linking the cluster to the hydrophobic pocket of a virus via a lipid-like pocket factor. We have estimated the binding affinities of three different pocket factors of echovirus 1 (EV1) in molecular dynamics simulations combined with non-equilibrium free-energy calculations. Read More

    Detection of Plasmodium Lactate Dehydrogenase Antigen in Buffer Using Aptamer-Modified Magnetic Microparticles for Capture, Oligonucleotide-Modified Quantum Dots for Detection, and Oligonucleotide-Modified Gold Nanoparticles for Signal Amplification.
    Bioconjug Chem 2017 Sep 15;28(9):2230-2234. Epub 2017 Aug 15.
    Department of Materials Science and Engineering, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
    To overcome the limitations associated with antibody-based sensors, we describe a proof-of-concept of an aptamer-based sandwich assay for detection of lactate dehydrogenase, an antigen associated with malaria. We show a detection limit of Plasmodium falciparum lactate dehydrogenase and Plasmodium vivax lactate dehydrogenase of 0.5 fmole in buffer, comparable to an antibody-based assay, using a magnetic particle-aptamer construct for capture and a quantum dot-aptamer construct for detection. Read More

    Multifunctional αvβ6 Integrin-Specific Peptide-Pt(IV) Conjugates for Cancer Cell Targeting.
    Bioconjug Chem 2017 Sep 10;28(9):2429-2439. Epub 2017 Aug 10.
    Faculty of Chemistry, Institute of Biological Chemistry, University of Vienna , Währinger Straße 38, 1090 Vienna, Austria.
    Increasing the specificity of cancer therapy, and thereby decreasing damage to normal cells, requires targeting to cancer-cell specific features. The αvβ6 integrin is a receptor involved in cell adhesion and is frequently up-regulated in cancer cells compared to normal cells. We have selected a peptide ligand reported to bind specifically to the β6 integrin and have synthesized a suite of multispecific molecules to explore the potential for targeting of cancer cells. Read More

    Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin.
    Bioconjug Chem 2017 Aug 22. Epub 2017 Aug 22.
    National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, PR China.
    As one of the pathogen-associated molecular patterns (PAMPs), flagellin is recently utilized as a potent adjuvant for many subunit vaccines. In this study, a truncated flagellin (tFL) with deletion of the hypervariable regions was adopted as a carrier-adjuvant by chemical conjugation with a chimeric malaria antigen M.RCAg-1 (M312) via a heterobifunctional polyethylene glycol (PEG) linker. Read More

    Fluorescent Functionalization across Quaternary Structure in a Virus-like Particle.
    Bioconjug Chem 2017 Sep 22;28(9):2277-2283. Epub 2017 Aug 22.
    Department of Chemistry and Biochemistry, ‡Department of Biological Sciences, and §School of Behavioral and Brain Sciences, University of Texas at Dallas , Richardson, Texas 75080, United States.
    Proteinaceous nanomaterials and, in particular, virus-like particles (VLPs) have emerged as robust and uniform platforms that are seeing wider use in biomedical research. However, there are a limited number of bioconjugation reactions for functionalizing the capsids, and very few of those involve functionalization across the supramolecular quaternary structure of protein assemblies. In this work, we exploit the recently described dibromomaleimide moiety as part of a bioconjugation strategy on VLP Qβ to break and rebridge the exposed and structurally important disulfides in good yields. Read More

    Improving the Imaging Contrast of (68)Ga-PSMA-11 by Targeted Linker Design: Charged Spacer Moieties Enhance the Pharmacokinetic Properties.
    Bioconjug Chem 2017 Sep 24;28(9):2485-2492. Epub 2017 Aug 24.
    Division of Radiopharmaceutical Development, German Cancer Consortium (DKTK) Freiburg, Department of Nuclear Medicine, Faculty of Medicine, Medical Center - University of Freiburg , Hugstetter Straße 55, 79106 Freiburg, Germany.
    (68)Ga-Glu-urea-Lys-(Ahx)-HBED-CC ((68)Ga-PSMA-11) represents a successful radiopharmaceutical for PET/CT imaging of prostate cancer. Further optimization of the tumor-to-background contrast might significantly enhance the sensitivity of PET/CT imaging and the probability of detecting recurrent prostate cancer at low PSA values. This study describes the advantage of histidine (H)/glutamic acid (E) and tryptophan (W)/glutamic acid (E) containing linkers on the pharmacokinetic properties of (68)Ga-PSMA-11. Read More

    Supramolecular Self-Assembly Bioinspired Synthesis of Luminescent Gold Nanocluster-Embedded Peptide Nanofibers for Temperature Sensing and Cellular Imaging.
    Bioconjug Chem 2017 Sep 16;28(9):2224-2229. Epub 2017 Aug 16.
    Center for Nano Energy Materials, School of Materials Science and Engineering, Northwestern Polytechnical University , Xi'an 710072, China.
    Metal nanoclusters (NCs) hold great potential as novel luminescent nanomaterials in many applications, while the synthesis of highly luminescent metal NCs still remains challenging. In this work, we report self-assembling peptides as a novel bioinspired scaffold capable of significantly enhancing the luminescence efficiency of gold nanoclusters (AuNCs). The resulting AuNCs capped with motif-designed peptides can self-assemble to form nanofiber structures, in which the luminescence of AuNCs is enhanced nearly 70-fold, with 21. Read More

    Stoichiometry and Dispersity of DNA Nanostructures Using Photobleaching Pair-Correlation Analysis.
    Bioconjug Chem 2017 Sep 22;28(9):2340-2349. Epub 2017 Aug 22.
    Department of Physics, McGill University , 3600 University Street, Montreal, Quebec H3A 0B8, Canada.
    A wide variety of approaches have become available for the fabrication of nanomaterials with increasing degrees of complexity, precision, and speed while minimizing cost. Their quantitative characterization, however, remains a challenge. Analytical methods to better inspect and validate the structure and composition of large nanoscale objects are required to optimize their applications in diverse technologies. Read More

    Systemic Delivery of Folate-PEG siRNA Lipopolyplexes with Enhanced Intracellular Stability for In Vivo Gene Silencing in Leukemia.
    Bioconjug Chem 2017 Sep 24;28(9):2393-2409. Epub 2017 Aug 24.
    Department of Pharmacy and Center for NanoScience, Ludwig-Maximilians-Universität München , Butenandtstr. 5-13, 81377 Munich, Germany.
    Protection of small interfering RNA (siRNA) against degradation and targeted delivery across the plasma and endosomal membranes to the final site of RNA interference (RNAi) are major aims for the development of siRNA therapeutics. Targeting for folate receptor (FR)-expressing tumors, we optimized siRNA polyplexes by coformulating a folate-PEG-oligoaminoamide (for surface shielding and targeting) with one of three lipo-oligoaminoamides (optionally tyrosine-modified, for optimizing stability and size) to generate ∼100 nm targeted lipopolyplexes (TLPs), which self-stabilize by cysteine disulfide cross-links. To better understand parameters for improved tumor-directed gene silencing, we analyzed intracellular distribution and siRNA release kinetics. Read More

    Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation.
    Bioconjug Chem 2017 Sep 24;28(9):2316-2326. Epub 2017 Aug 24.
    Department of Pediatrics, Section of Hematology/Oncology, University of Chicago , 900 East 57th Street, KCBD 5122, Chicago, Illinois 60637, United States.
    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein-protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. Read More

    "Polymultivalent" Polymer-Peptide Cluster Conjugates for an Enhanced Targeting of Cells Expressing αvβ3 Integrins.
    Bioconjug Chem 2017 Sep 21;28(9):2241-2245. Epub 2017 Aug 21.
    Univ Lyon, Université Lyon 1 , INSA de Lyon, CNRS, Laboratoire Ingénierie des Matériaux Polymères, UMR5223, F-69621 Villeurbanne, France.
    A new class of "polymultivalent" ligands combining several ligand clusters and a water-soluble biocompatible polymer is introduced. These original conjugates bear two levels of multivalency. They are prepared by covalent coupling of a controlled number of tetrameric cRGD peptide clusters along a well-defined copolymer synthesized by RAFT polymerization. Read More

    (89)Zr-Immuno-Positron Emission Tomography in Oncology: State-of-the-Art (89)Zr Radiochemistry.
    Bioconjug Chem 2017 Sep 24;28(9):2211-2223. Epub 2017 Aug 24.
    Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR6302, CNRS, Université Bourgogne Franche-Comté , F-21000 Dijon, France.
    Immuno-positron emission tomography (immunoPET) with (89)Zr-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. Read More

    New Trends and current status of PET and SPECT radioligands for Neuronal 5-HT Receptors (5-HTRs) and serotonin transporter (SERT).
    Bioconjug Chem 2017 Aug 2. Epub 2017 Aug 2.
    The critical role of serotonin (5-hydroxytryptamine; 5-HT) and its receptors (5-HTRs) in the pathophysiology of various neuropsychiatric and neurodegenerative disorders render them attractive diagnostic/therapeutic targets for brain disorders. Therefore, in vivo assessment of binding of 5-HT receptor ligands under a multitude of physiologic and pathologic scenario may support the more accurate identification of disease and its progression, patient's response to therapy, and the screening of novel therapeutic strategies. The present review aims to focus on the current status of radioligands used for positron emission tomography and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors. Read More

    Selective Binders of the Tandem Src Homology 2 Domains in Syk and Zap70 Protein Kinases by DNA-Programmed Spatial Screening.
    Bioconjug Chem 2017 Sep 30;28(9):2384-2392. Epub 2017 Aug 30.
    Institut für Chemie, Humboldt-Universität zu Berlin , Brook-Taylor-Straße 2, D-12489 Berlin, Germany.
    Members of the Syk family of tyrosine kinases arrange Src homology 2 (SH2) domains in tandem to allow the firm binding of immunoreceptor tyrosine-based interaction motifs (ITAMs). While the advantages provided by the bivalency enhanced interactions are evident, the impact on binding specificity is less-clear. For example, the spleen tyrosine kinase (Syk) and the ζ-chain-associated protein kinase (ZAP-70) recognize the consensus sequence pYXXI/L(X)6-8 pYXXI/L with near-identical nanomolar affinity. Read More

    Osteoconductive Amine-Functionalized Graphene-Poly(methyl methacrylate) Bone Cement Composite with Controlled Exothermic Polymerization.
    Bioconjug Chem 2017 Sep 21;28(9):2254-2265. Epub 2017 Aug 21.
    Department of Chemistry, Banaras Hindu University , Varanasi 221005, India.
    Bone cement has found extensive usage in joint arthroplasty over the last 50 years; still, the development of bone cement with essential properties such as high fatigue resistance, lower exothermic temperature, and bioactivity has been an unsolved problem. In our present work, we have addressed all of the mentioned shortcomings of bone cement by reinforcing it with graphene (GR), graphene oxide (GO), and surface-modified amino graphene (AG) fillers. These nanocomposites have shown hypsochromic shifts, suggesting strong interactions between the filler material and the polymer matrix. Read More

    GlcNAc Conjugated Atorvastatin with Enhanced Water Solubility and Cellular Internalization.
    Bioconjug Chem 2017 Aug 7;28(8):2109-2113. Epub 2017 Aug 7.
    Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, ‡Department of Biomedical Engineering, §The Center for Clinical and Translational Science, ∥The Comprehensive Cancer Center, ⊥Dorothy M. Davis Heart & Lung Research Institute, and ¶Department of Radiation Oncology, The Ohio State University , Columbus, Ohio 43210, United States.
    Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Read More

    Selecting a DNA-Encoded Chemical Library against Non-immobilized Proteins Using a "Ligate-Cross-Link-Purify" Strategy.
    Bioconjug Chem 2017 Sep 10;28(9):2293-2301. Epub 2017 Aug 10.
    Department of Chemistry, The University of Hong Kong , Pokfulam Road, Hong Kong SAR, China.
    DNA-encoded chemical libraries (DELs) have recently emerged and become an important technology platform in biomedical research and drug discovery. DELs containing large numbers of compounds can be prepared and selected against biological targets to discover novel ligands and inhibitors. In practice, DELs are usually selected against purified and immobilized proteins using the typical "bind-wash-elute" protocol; however, selection methods compatible with non-immobilized proteins would be able to greatly expand the target scope of DELs beyond purified proteins to more-complex and biologically relevant targets. Read More

    Amphiphilic Peptide Nanorods Based on Oligo-Phenylalanine as a Biocompatible Drug Carrier.
    Bioconjug Chem 2017 Sep 11;28(9):2266-2276. Epub 2017 Aug 11.
    Department of Biochemistry, College of Natural Sciences, Chungnam National University , 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Republic of Korea.
    Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH3F8 (Arg-His3-Phe8), as a drug-delivery carrier. Read More

    Complex Consisting of β-Glucan and Antigenic Peptides with Cleavage Site for Glutathione and Aminopeptidases Induces Potent Cytotoxic T Lymphocytes.
    Bioconjug Chem 2017 Sep 9;28(9):2246-2253. Epub 2017 Aug 9.
    Department of Chemistry and Biochemistry, The University of Kitakyushu , 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
    The efficient induction of antigen-specific immune responses requires not only promotion of the uptake of antigens and adjuvant molecules into antigen-presenting cells but also control of their intracellular behavior. We previously demonstrated that the β-glucan schizophyllan (SPG) can form complexes with CpG oligonucleotides with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses. In this study, we prepared various conjugates composed of antigenic peptide (OVA257-264) and dA40 and made complexes with SPG. Read More

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