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    5319 results match your criteria Bioconjugate Chemistry [Journal]

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    Photocontrolled Release of Doxorubicin Conjugated through a Thioacetal Photocage in Folate-Targeted Nanodelivery Systems.
    Bioconjug Chem 2017 Nov 17. Epub 2017 Nov 17.
    Despite their proven ability for precise and targeted release, nanoplatform systems for photocontrolled delivery often face formidable synthetic challenges, in part, due to the paucity of advanced linker strategies. Here we report on a novel linker strategy using a thioacetal ortho-nitrobenzaldehyde (TNB) cage, demonstrating its application for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable linker, TNB(OH), which presents two identical arms, each terminated with a hydroxyl functionality, was prepared in a single step from 6-nitroverataldehyde. Read More

    Conjugation of transforming growth factor beta to antigen-loaded poly(lactide-co-glycolide) nanoparticles enhances efficiency of antigen-specific tolerance.
    Bioconjug Chem 2017 Nov 17. Epub 2017 Nov 17.
    Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v. Read More

    A Novel Approach for 99mTc-Labeling of Red Blood Cells: Evaluation of 99mTc-4SAboroxime as a Blood Pool Imaging Agent.
    Bioconjug Chem 2017 Nov 17. Epub 2017 Nov 17.
    Angiography with radiolabeled red blood cells (RBCs) plays an important role in diagnosis and prognosis in vascular diseases. Both in vitro and in vivo methods have been developed for 99mTc-labeling of RBCs. However, these methods are complicated and lack of reproducibility. Read More

    Designing Dendron-Polymer Conjugate Based Targeted Drug Delivery Platforms with a 'Mix-and-Match' Modularity.
    Bioconjug Chem 2017 Nov 14. Epub 2017 Nov 14.
    Polymeric micellar systems are emerging as a very important class of nano-pharmaceuticals due to their ability to improve pharmacokinetics and bio-distribution of chemotherapy drugs, as well as to reduce related systemic toxicities. While these nano sized delivery systems inherently benefit from passive targeting through the enhanced permeation and retention effect leading to increased accumulation in the tumor, additional active targeting can be achieved through surface modification of micelles with targeting groups specific for over-expressed receptors of tumor cells. In this project, non-toxic, biodegradable, and modularly tunable micellar delivery systems were generated using two types of dendron-polymer conjugates. Read More

    Rational design and synthesis of post-functionalizable peptide foldamers as helical templates.
    Bioconjug Chem 2017 Nov 14. Epub 2017 Nov 14.
    We herein developed post-functionalizable helical peptides composed of Leu, Aib, and Azl residues. We show that the synthesized peptides 1 and 2 form helical structures, and may be modified using specific side chain or several functional groups by the click reaction without influencing their secondary structures. Read More

    Primary amine-clustered DNA aptamer for DNA-protein conjugation catalyzed by microbial transglutaminase.
    Bioconjug Chem 2017 Nov 13. Epub 2017 Nov 13.
    DNA-protein conjugates are promising biomolecules for use in areas ranging from therapeutics to analysis because of the dual functionalities of DNA and protein. Conjugation requires site-specific and efficient covalent bond formation without impairing the activity of both biomolecules. Herein, we have focused on the use of a microbial transglutaminase (MTG) that catalyzes the cross-linking reaction between a glutamine residue and a primary amine. Read More

    Metal-free Cycloaddition Chemistry Driven Pretargeted Radioimmunotherapy Using α-Particle Radiation.
    Bioconjug Chem 2017 Nov 12. Epub 2017 Nov 12.
    The pretargeted radioimmunotherapy approach (PRIT) decouples the administration of tumor targeting monoclonal antibodies (mAb) from that of the radiolabeled ligand. This multi-step strategy allows delivery of high doses of radiation to tumor cells while minimizing non-specific normal tissue irradiation. In this study, we evaluated the potential of pretargeted α-particle radioimmunotherapy based on inverse electron demand Diels-Alder reaction (IEDAA) between trans-cyclooctene (TCO) and tetrazine (Tz). Read More

    Imaging PD-L1 Expression with ImmunoPET.
    Bioconjug Chem 2017 Nov 15. Epub 2017 Nov 15.
    Department of Radiology and Biomedical Imaging, ‡Department of Medicine, §Helen Diller Family Comprehensive Cancer Center, ∥Department of Pharmaceutical Chemistry, and ⊥Department of Radiation Oncology, University of California, San Francisco , 505 Parnassus Avenue, San Francisco, California 94143, United States.
    High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that (89)Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy. Read More

    Variability of Complement Response toward Preclinical and Clinical Nanocarriers in the General Population.
    Bioconjug Chem 2017 Nov 1;28(11):2747-2755. Epub 2017 Nov 1.
    Translational Bio-Nanosciences Laboratory, ‡Colorado Center for Nanomedicine and Nanosafety, §The Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, ∥Systems Genetics and Bioinformatics Laboratory, and ⊥Center for Translational Pharmacokinetics and Pharmacogenomics, University of Colorado Anschutz Medical Campus, 12850 East Montview Blvd., Aurora, Colorado 80045, United States.
    Opsonization (coating) of nanoparticles with complement C3 component is an important mechanism that triggers immune clearance and downstream anaphylactic and proinflammatory responses. The variability of complement C3 binding to nanoparticles in the general population has not been studied. We examined complement C3 binding to dextran superparamagnetic iron oxide nanoparticles (superparamagnetic iron oxide nanoworms, SPIO NWs, 58 and 110 nm) and clinically approved nanoparticles (carboxymethyl dextran iron oxide ferumoxytol (Feraheme, 28 nm), highly PEGylated liposomal doxorubicin (LipoDox, 88 nm), and minimally PEGylated liposomal irinotecan (Onivyde, 120 nm)) in sera from healthy human individuals. Read More

    Facile Formation of Gold-Nanoparticle-Loaded γ-Polyglutamic Acid Nanogels for Tumor Computed Tomography Imaging.
    Bioconjug Chem 2017 Nov 3;28(11):2692-2697. Epub 2017 Nov 3.
    Department of Radiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University , Shanghai 200072, People's Republic of China.
    The formation of gold nanoparticle (Au NP)-loaded γ-polyglutamic acid (γ-PGA) nanogels (NGs) for computed tomography (CT) imaging of tumors is reported. γ-PGA with carboxyl groups activated by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride is first emulsified to form NGs and then in situ chemically cross-linked with polyethylenimine (PEI)-entrapped Au NPs with partial polyethylene glycol (PEG) modification ([(Au(0))200-PEI·NH2-mPEG]). The formed γ-PGA-[(Au(0))200-PEI·NH2-mPEG] NGs with a size of 108. Read More

    Tethering of Chemotherapeutic Drug/Imaging Agent to Bile Acid-Phospholipid Increases the Efficacy and Bioavailability with Reduced Hepatotoxicity.
    Bioconjug Chem 2017 Nov 9. Epub 2017 Nov 9.
    Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology , NCR Biotech Science Cluster, 3rd Milestone Faridabad-Gurgaon Expressway, Faridabad, Haryana 121001, India.
    Weakly basic drugs display poor solubility and tend to precipitate in the stomach's acidic environment causing reduced oral bioavailability. Tracing of these orally delivered therapeutic agents using molecular probes is challenged due to their poor absorption in the gastrointestinal tract (GIT). Therefore, we designed a gastric pH stable bile acid derived amphiphile where Tamoxifen (as a model anticancer drug) is conjugated to lithocholic acid derived phospholipid (LCA-Tam-PC). Read More

    Last-Step Pd-Mediated [(11)C]CO Labeling of a Moxestrol-Conjugated o-Iodobenzyl Alcohol: From Model Experiments to in Vivo Positron Emission Tomography Studies.
    Bioconjug Chem 2017 Nov 27;28(11):2887-2894. Epub 2017 Oct 27.
    University of Bordeaux, CNRS, Institut des Sciences Moléculaires, UMR 5255 , 351 Cours de la Libération, 33405 Talence Cedex, France.
    The fast, efficient, and functional group tolerant last-step radiolabeling of bioconjugates is crucial for positron emission tomography (PET) applications. In this context, o-iodobenzyl alcohol based structures were identified as ideal tags for an easy Pd-catalyzed carbonylation after bioconjugation, and a moxestrol-conjugated precursor was chosen as the model compound for the further studies. Despite scale and time constraints, conditions developed with [(12)C]CO and [(13)C]CO were easily transferred to the (11)C isotope, and the desired radioactive product was obtained in amounts up to 740 MBq with radiochemical purities higher than 99%. Read More

    Carbon Nanotube as a Tool for Fighting Cancer.
    Bioconjug Chem 2017 Nov 7. Epub 2017 Nov 7.
    Department of Microbiology and Immunology, Laboratory of Tumor Immunology and ‡Department of Chemistry and Biochemistry, Institute of Biosciences, São Paulo State University (UNESP) , 18618-691 Botucatu, Sao Paulo Brazil.
    In 2015, cancer was the cause of almost 22% of deaths worldwide. The high frequency of relapsing diseases and metastasis requires the development of new diagnostic and therapeutic approaches, and the use of nanomaterials is a promising tool for fighting cancer. Among the more extensively studied nanomaterials are carbon nanotubes (CNTs), synthesized as graphene sheets, whose spiral shape is varied in length and thickness. Read More

    Enzymatic Installation of Functional Molecules on Amyloid-Based Polymers.
    Bioconjug Chem 2017 Nov 3;28(11):2687-2691. Epub 2017 Nov 3.
    Department of Applied Chemistry, Graduate School of Science and Engineering, University of Toyama , 3190 Gofuku, Toyama 930-8555, Japan.
    We produced a functional polymer whose framework comprised transthyretin (TTR) amyloid fibrils. In order to immobilize functional molecules onto the amyloid fibrils, transpeptidase sortase A (srtA), which catalyzes the covalent binding of LPXTG with polyglycine, was employed. After the preparation of the amyloid fibril of LPETGG-tagged TTR, immobilization of Gly5-fused GFP on the amyloid fibrils by srtA-mediated transpeptidation was carried out. Read More

    Unlocking Endosomal Entrapment with Supercharged Arginine-Rich Peptides.
    Bioconjug Chem 2017 Nov 13. Epub 2017 Nov 13.
    Department of Biochemistry and Biophysics, ⊥Program in Integrative Nutrition & Complex Diseases, Department of Nutrition and Food Science, and §Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
    Endosomal entrapment is a common bottleneck in various macromolecular delivery approaches. Recently, the polycationic peptide dfTAT was identified as a reagent that induces the efficient leakage of late endosomes and, thereby, enhances the penetration of macromolecules into the cytosol of live human cells. To gain further insights into the features that lead to this activity, the role of peptide sequence was investigated. Read More

    Fluorogenic Protein Labeling Probes to Study the Morphological Interplay between PreLamin and Mature Lamin.
    Bioconjug Chem 2017 Nov 3;28(11):2895-2902. Epub 2017 Nov 3.
    Department of Chemistry and ‡Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University , 101 Sec. 2, Kuang Fu Rd, Hsinchu 30013, Taiwan (ROC).
    Although many protein labeling probes have been developed to elucidate the trafficking and turnover processes of cell surface proteins, real-time tracking of intracellular proteins remains a challenging task. Herein, we describe a new design to construct a cell-permeable, photostable, and far-red fluorescent turn-on probe to enable no-wash, organelle-specific, and long-term visualization of intracellular SNAP-tagged proteins in living cells. When the probe was used in dual-color pulse chase labeling experiments to differentiate between preLamin and mature Lamin, our results reveal that the shape of mature Lamin can be altered by the newly synthesized preLamin and that this alteration is progressive, cumulative, and due to a concentration-dependent dominant-negative effect of preLamin. Read More

    Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor.
    Bioconjug Chem 2017 Nov 31;28(11):2841-2848. Epub 2017 Oct 31.
    State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , 1 North Second Street, Zhong-Guan Village, Beijing 100190, PR China.
    In this paper, we reported a novel strategy for the site-specific attachment of polyethylene glycol (PEGylation) of proteins using elevated hydrostatic pressure. The process was similar to the conventional one except the reactor was under elevated hydrostatic pressure. The model protein was recombinant human ciliary neurotrophic factor (rhCNTF), and the reagent was monomethoxy-polyethylene glycol-maleimide (mPEG-MAL). Read More

    Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications.
    Bioconjug Chem 2017 Nov 23;28(11):2772-2783. Epub 2017 Oct 23.
    Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University , Fargo, North Dakota 58105, United States.
    The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Read More

    Tuning the Multifunctionality of Iron Oxide Nanoparticles Using Self-Assembled Mixed Lipid Layers.
    Bioconjug Chem 2017 Nov 30;28(11):2729-2736. Epub 2017 Oct 30.
    Department of Chemical Engineering, University of Rhode Island , 51 Lower College Road, Kingston, Rhode Island 02881, United States.
    We present an approach to tuning the multifunctionality of iron oxide nanoparticles (IONs) using mixed self-assembled monolayers of cationic lipid and anionic polyethylene glycol (PEG) lipid. By forming stable, monodispersed lipid-coated IONs (L-IONs) through a solvent-exchange technique, we were able to demonstrate the relationship between surface charge, the magnetic transverse relaxivity (r2 from T2-weighted images), and the binding capacity of small interfering ribonucleic acids (siRNAs) as a function of the cationic-to-anionic (PEG) lipid ratio. These properties were controlled by the cationic charge and the PEG conformation; relaxivity and siRNA binding could be varied in the mushroom and brush regimes but not at high brush densities. Read More

    Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.
    Bioconjug Chem 2017 Nov 27;28(11):2874-2886. Epub 2017 Oct 27.
    Center for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute Johns Hopkins University School of Medicine , Baltimore, Maryland 21231, United States.
    Brain-related disorders have outmatched cancer and cardiovascular diseases worldwide as the leading cause of morbidity and mortality. The lack of effective therapies and the relatively dry central nervous system (CNS) drug pipeline pose formidable challenge. Superior, targeted delivery of current clinically approved drugs may offer significant potential. Read More

    Improved Photoinduced Fluorogenic Alkene-Tetrazole Reaction for Protein Labeling.
    Bioconjug Chem 2017 Nov 26;28(11):2859-2864. Epub 2017 Oct 26.
    Department of Chemistry, ‡Department of Chemistry, Nebraska Center for Materials and Nanoscience, and Center for Integrated Biomolecular Communication, and §Department of Chemical & Biomolecular Engineering, University of Nebraska-Lincoln , Lincoln, Nebraska 68588, United States.
    The 1,3-dipolar cycloaddition reaction between an alkene and a tetrazole represents one elegant and rare example of fluorophore-forming bioorthogonal chemistry. This is an attractive reaction for imaging applications in live cells that requires less intensive washing steps and/or needs spatiotemporal resolutions. In the present work, as an effort to improve the fluorogenic property of the alkene-tetrazole reaction, an aromatic alkene (styrene) was investigated as the dipolarophile. Read More

    Preparation of Tc99m-Labeled Pseudomonas Bacteriophage without Adversely Impacting Infectivity or Biodistribution.
    Bioconjug Chem 2017 Nov 26;28(11):2698-2706. Epub 2017 Oct 26.
    Department of Radiology, Division of Pediatric Radiology and Nuclear Medicine, Lucile Packard Children's Hospital , Stanford, California 94305, United States.
    Bacteriophages (phages) are ubiquitous viruses which have adapted to infect and replicate within target bacteria, their only known hosts, in a strain specific fashion with minimal cross infectivity. The recent steep rise in antibiotic resistance throughout the world has renewed interest in adapting phages for the imaging and treatment of bacterial infection in humans. In this article, we describe the current limitations surrounding the radiolabeling of phage for the imaging and treatment of bacterial infection and methods to overcome these difficulties. Read More

    Less is More: A Comparison of Antibody-Gold Nanoparticle Conjugates of Different Ratios.
    Bioconjug Chem 2017 Nov 20;28(11):2737-2746. Epub 2017 Oct 20.
    A.N. Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences , Moscow 119071, Russia.
    This comprehensive study is related to gold nanoparticles (GNPs) conjugated with antibodies. The goal of the study is to determine the minimal concentration of antibodies for conjugate synthesis when the conjugates have high antigen-capturing activity. Two systems were studied: gold nanoparticles conjugated with monoclonal antibodies (mAb-GNP) specific to Helicobacter pylori and gold nanoparticles conjugated with polyclonal antibodies (pAb-GNP) specific to mouse immunoglobulins. Read More

    Tailored Multivalent Neo-Glycoproteins: Synthesis, Evaluation, and Application of a Library of Galectin-3-Binding Glycan Ligands.
    Bioconjug Chem 2017 Nov 18;28(11):2832-2840. Epub 2017 Oct 18.
    Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University , Pauwelsstrasse 20, 52074 Aachen, Germany.
    Galectin-3 (Gal-3), a member of the β-galactoside-binding lectin family, is a tumor biomarker and involved in tumor angiogenesis and metastasis. Gal-3 is therefore considered as a promising target for early cancer diagnosis and anticancer therapy. We here present the synthesis of a library of tailored multivalent neo-glycoproteins and evaluate their Gal-3 binding properties. Read More

    Metal-Organic Frameworks@Polymer Composites Containing Cyanines for Near-Infrared Fluorescence Imaging and Photothermal Tumor Therapy.
    Bioconjug Chem 2017 Nov 16;28(11):2784-2793. Epub 2017 Oct 16.
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , 5625 Renmin Street, Changchun, Jilin 130022, P. R. China.
    As a noninvasive treatment method, photothermal therapy (PTT) has been widely investigated for cancer therapy. In this work, metal-organic frameworks@polymer composites (UiO-66@CyP) with bioimaging and PTT activity were prepared by introducing cyanine-containing polymer (CyP) via multicomponent Passerini reaction in the presence of Zr-based nanoscale metal-organic frameworks (UiO-66). As-prepared UiO-66@CyP not only possesses uniformed size, controllable morphology, and excellent dispersibility in aqueous media, but also indicates strong near-infrared absorption and high photothermal conversion efficiency. Read More

    Ultrasmall Paramagnetic Iron Oxide Nanoprobe Targeting Epidermal Growth Factor Receptor for In Vivo Magnetic Resonance Imaging of Hepatocellular Carcinoma.
    Bioconjug Chem 2017 Nov 20;28(11):2794-2803. Epub 2017 Oct 20.
    Department of Internal Medicine, ‡Department of Biomedical Engineering, §Department of Radiology, ∥Department of Biostatistics, ⊥Department of Pathology, and #Department of Mechanical Engineering, University of Michigan , Ann Arbor, Michigan 48109, United States.
    Hepatocellular carcinoma (HCC) is a common worldwide cancer that is rising rapidly in incidence. MRI is a powerful noninvasive imaging modality for HCC detection, but lack of specific contrast agents limits visualization of small tumors. EGFR is frequently overexpressed in HCC and is a promising target. Read More

    Polyethylene Glycol Based Changes to β-Sheet Protein Conformational and Proteolytic Stability Depend on Conjugation Strategy and Location.
    Bioconjug Chem 2017 Oct 9;28(10):2507-2513. Epub 2017 Oct 9.
    Department of Chemistry and Biochemistry, Brigham Young University , Provo, Utah 84602, United States.
    The development of chemical strategies for site-specific protein modification now enables researchers to attach polyethylene glycol (PEG) to a protein drug at one or more specific locations (i.e., protein PEGylation). Read More

    Self-Assembled Tumor-Penetrating Peptide-Modified Poly(l-γ-glutamylglutamine)-Paclitaxel Nanoparticles Based on Hydrophobic Interaction for the Treatment of Glioblastoma.
    Bioconjug Chem 2017 Nov 10;28(11):2823-2831. Epub 2017 Oct 10.
    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.
    To enhance the tumor-penetrating ability and targeting therapeutic effect of polymer-drug conjugates (PDCs), tumor-penetrating peptide RGERPPR (RGE) modified and PEGylated poly(l-γ-glutamylglutamine)-paclitaxel (PGG-PTX) nanoparticles (RGE-PEG/PGG-PTX NPs) were prepared by using a so-called "modular" design strategy. In brief, a RGERPPR-conjugated targeting material, DSPE-PEG-RGERPPR, was first synthesized and assembled with PGG-PTX into RGE-PEG/PGG-PTX NPs based on the hydrophobic interaction between the groups of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and PTX. The NPs exhibited a uniform spherical morphology with particle size of around 90 nm, as shown by the dynamic light scattering and transmission electron microscopy results. Read More

    Facile Preparation of Doxorubicin-Loaded and Folic Acid-Conjugated Carbon Nanotubes@Poly(N-vinyl pyrrole) for Targeted Synergistic Chemo-Photothermal Cancer Treatment.
    Bioconjug Chem 2017 Nov 13;28(11):2815-2822. Epub 2017 Oct 13.
    School of Science, State Key Laboratory for Mechanical Behavior of Materials, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University , Xi'an 710049, China.
    We developed a bifunctional nanoplatform for targeted synergistic chemo-photothermal cancer treatment. The nanoplatform was constructed through a facile method in which poly(N-vinyl pyrrole) (PVPy) was coated on cut multiwalled carbon nanotubes (c-MWNTs); FA-PEG-SH was then linked by thiol-ene click reaction to improve the active targeting ability, water dispersibility, and biocompatibility and to extend the circulation time in blood. The PVPy shell not only enhanced the photothermal effect of c-MWNTs significantly but also provided a surface that could tailor targeting molecules and drugs. Read More

    Polyplex Micelle with pH-Responsive PEG Detachment and Functional Tetraphenylene Incorporation to Promote Systemic Gene Expression.
    Bioconjug Chem 2017 Nov 10;28(11):2849-2858. Epub 2017 Oct 10.
    School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin University of Technology , Tianjin 300384, P. R. China.
    Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. Read More

    Toward Personalized Peptide-Based Cancer Nanovaccines: A Facile and Versatile Synthetic Approach.
    Bioconjug Chem 2017 Nov 13;28(11):2756-2771. Epub 2017 Oct 13.
    Department of Biomedical Engineering, University of California , Davis, California 95616, United States.
    Personalized cancer vaccines (PCVs) are receiving attention as an avenue for cancer immunotherapy. PCVs employ immunogenic peptide epitopes capable of stimulating the immune system to destroy cancer cells with great specificity. Challenges associated with effective delivery of these peptides include poor solubility of hydrophobic sequences, rapid clearance, and poor immunogenicity, among others. Read More

    Microenvironmental Control of MUC1 Aptamer-Guided Acid-Labile Nanoconjugate within Injectable Microporous Hydrogels.
    Bioconjug Chem 2017 Oct 5;28(10):2530-2537. Epub 2017 Oct 5.
    Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University , Nanjing 210009, PR China.
    Although aptamers are well-known as cell-specific membrane biomarkers for tumor-targeted therapy, it is important to avoid their degradation by nucleases in vivo. In this study, we developed a MUC1 aptamer-doxorubicin nanoconjugate (APT-DOX) through an acid-labile linkage and embedded APT-DOX into a thermosensitive hydrogel for antitumor therapy. The hydrogels exhibit a sol-gel transition upon intratumoral injection, resulting in the protection and controlled release control of APT-DOX with the shielding of the gel network. Read More

    Multifunctional Magnetic and Upconverting Nanobeads as Dual Modal Imaging Tools.
    Bioconjug Chem 2017 Nov 2;28(11):2707-2714. Epub 2017 Nov 2.
    Istituto Italiano di Tecnologia , Via Morego 30, 16163 Genova, Italy.
    We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. Read More

    Evaluation of a Centyrin-Based Near-Infrared Probe for Fluorescence-Guided Surgery of Epidermal Growth Factor Receptor Positive Tumors.
    Bioconjug Chem 2017 Nov 17;28(11):2865-2873. Epub 2017 Oct 17.
    Janssen Research & Development , 1400 McKean Road, Springhouse, Pennsylvania 19477, United States.
    Tumor-targeted near-infrared fluorescent dyes have the potential to improve cancer surgery by enabling surgeons to locate and resect more malignant lesions where good visualization tools are required to ensure complete removal of malignant tissue. Although the tumor-targeted fluorescent dyes used in humans to date have been either small organic molecules or high molecular weight antibodies, low molecular weight protein scaffolds have attracted significant attention because they penetrate solid tumors almost as efficiently as small molecules, but can be infinitely mutated to bind almost any antigen. Here we describe the use of a 10 kDa protein scaffold, a Centyrin, to target a near-infrared fluorescent dye to tumors that overexpress the epidermal growth factor receptor (EGFR) for fluorescence-guided surgery (FGS). Read More

    Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo.
    Bioconjug Chem 2017 Nov 12;28(11):2715-2728. Epub 2017 Oct 12.
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy , Los Angeles, California 90089, United States.
    Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains. Read More

    Polymer Conjugation to Enhance Cellulase Activity and Preserve Thermal and Functional Stability.
    Bioconjug Chem 2017 Oct 5;28(10):2638-2645. Epub 2017 Oct 5.
    Department of Chemistry and Biochemistry, 651 East High Street, Miami University , Oxford, Ohio 45056 United States.
    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 noncovalent interactions with the substrate. Read More

    Avidin/Biotin Bioinspired Platform for Dual In Vivo (18)F-PET/NIRF Molecular Imaging.
    Bioconjug Chem 2017 Oct 26;28(10):2524-2529. Epub 2017 Sep 26.
    IMIV, Service Hospitalier Frédéric Joliot, CEA, Inserm, Université Paris Sud, CNRS, Université Paris-Saclay , Orsay, France.
    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 [(18)F]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 Nov 20;28(11):2804-2814. Epub 2017 Oct 20.
    Department of Basic Medical Sciences, Western University of Health Sciences , Lebanon, Oregon 97355, United States.
    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 decreases effective pore sizes. Read More

    Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs.
    Bioconjug Chem 2017 Oct 22;28(10):2620-2626. 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 Oct 4;28(10):2599-2607. Epub 2017 Oct 4.
    Center of Translational Biomedicine, Skolkovo Institute of Science and Technology , Skolkovo, Moscow 143026, Russia.
    We developed a novel technique for the efficient conjugation of oligonucleotides with various alkyl azides such as fluorescent dyes, biotin, cholesterol, N-acetylgalactosamine (GalNAc), etc. using copper-catalysed alkyne-azide cycloaddition on the 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 Oct 6;28(10):2608-2619. Epub 2017 Oct 6.
    Institute of Nano-chemistry and Nano-biology, Shanghai University , Shanghai 200444, P.R. China.
    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 Oct 14;28(10):2518-2523. 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 Nov 26;28(11):2673-2686. Epub 2017 Sep 26.
    School of Chemical Sciences, The University of Auckland , Private Bag, 92019 Auckland, New Zealand.
    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, the combination of antimicrobial peptides (AMPs) and nanoparticles is a promising tool with which 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 Oct 22;28(10):2538-2548. 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 Immunoglobulin G1 Monoclonal Antibody Biotherapeutics.
    Bioconjug Chem 2017 Oct 28;28(10):2549-2559. Epub 2017 Sep 28.
    Department of Chemistry and ‡Department of Chemical Engineering, Indian Institute of Technology Delhi , New Delhi 110016, India.
    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 (-80 to -20 °C). However, reliable storage at these temperatures can be a challenge, particularly in developing and underdeveloped countries; hence, lately, there has been a renewed interest in creating formulations that would offer stability at higher temperatures (25 to 55 °C). Read More

    Amino Acid Functionalized Inorganic Nanoparticles as Cutting-Edge Therapeutic and Diagnostic Agents.
    Bioconjug Chem 2017 Sep 26. Epub 2017 Sep 26.
    Department of Immunology and Pathology, Central Clinical School, Monash University , Melbourne, Victoria 3004, Australia.
    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 Oct 13;28(10):2514-2517. 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 Oct 18;28(10):2581-2590. 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

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