6,264 results match your criteria Bioconjugate chemistry[Journal]


Localization of Therapeutic Fab-CHP Conjugates to Sites of Denatured Collagen for the Treatment of Rheumatoid Arthritis.

Bioconjug Chem 2020 Jul 1. Epub 2020 Jul 1.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in synovial joints and protease-induced cartilage degradation. Current biologic treatments for RA can effectively reduce symptoms, primarily by neutraliz-ing the proinflammatory cytokine TNFα; however, continued, indiscriminate over-inhibition of inflammatory factors can significantly weaken the host immune system, leading to opportunistic infections and interrupting treatment. We hypothesize that localizing anti-TNFα therapeutics to denatured collagen (dCol) present at arthritic joints, via conjugation with collagen-hybridizing peptides (CHPs), will reduce off-site antigen binding and maintain local immunosuppression. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00324DOI Listing

Complement Inhibitors Block Complement C3 Opsonization and Improve Targeting Selectivity of Nanoparticles in Blood.

Bioconjug Chem 2020 Jun 29. Epub 2020 Jun 29.

Division of Rheumatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.

Complement is one of the critical branches of innate immunity that determines the recognition of engineered nanoparticles by immune cells. Antibody-targeted iron oxide nanoparticles are a popular platform for magnetic separations, in vitro diagnostics, and molecular imaging. We used 60 nm cross-linked iron oxide nanoworms (CLIO NWs) modified with antibodies against Her2/neu and EpCAM, which are common markers of blood-borne cancer cells, to understand the role of complement in the selectivity of targeting of tumor cells in whole blood. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00342DOI Listing

Identification of a DNA aptamer that binds to human monocytes and macrophages.

Bioconjug Chem 2020 Jun 26. Epub 2020 Jun 26.

As cancer strategies shift toward immunotherapy, the need for new binding ligands to target and isolate specific immune cell populations has soared. Based on prior work identifying a peptide specific for murine M2-like macrophages, we sought to identify an aptamer that could bind human M2-like macrophages. Tumor-associated macrophage (TAMs) adopt an M2-like phenotype and support tumor progression and dissemination. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00247DOI Listing

Simultaneous targeting of two master regulators of apoptosis with dual-action PNA- and DNA-peptide conjugates.

Bioconjug Chem 2020 Jun 22. Epub 2020 Jun 22.

Conjugation of peptides with oligonucleotides offers opportunities for combining the strengths of both biopoly¬mer clas-ses. Herein we show that the combination of a peptide-based module with an antisense oligonucleotide module provides for enhancements of potency and a widened scope of cell delivery options. The peptide unit comprises a Smac mimetic compound (SMCs) which antagonizes the action of inhibitor of apoptosis proteins (IAPs) frequently overexpressed in cancer cells. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00284DOI Listing

Enabling Indium channels for Mass Cytometry by using reinforced cyclam-based chelating polylysine.

Bioconjug Chem 2020 Jun 22. Epub 2020 Jun 22.

The synthesis of a polylysine polymer functionalized with the previously reported astonishingly inert [In(cb-te2pa)] chelate was performed. A biotin end group allowed the conjugation to biotinylated beads by the intermediary of a Fluorescein isothiocyanate / neutravidin receptor. High quality Imaging Mass Cytometry trials, based on In detection were performed to highlight the behavior of the material. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00267DOI Listing

Optimized Methods for the Production and Bioconjugation of Site-Specific, Alkyne-Modified Glucagon-like Peptide-1 (GLP-1) Analogs to Azide-Modified Delivery Platforms Using Copper-Catalyzed Alkyne-Azide Cycloaddition.

Bioconjug Chem 2020 Jun 25. Epub 2020 Jun 25.

School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia.

This study aimed to develop and optimize chemistries to produce alkyne-modified glucagon-like peptide-1(7-36)-amide (GLP-1(7-36)-NH) libraries, which could be rapidly and efficiently conjugated to other components and screened to identify compounds with the best drug delivery properties, as potential treatments for type 2 diabetes or obesity. For this purpose, the Lys26 (K26) side-chain, and the amino (N)- and carboxy (C)-termini of a dipeptidyl peptidase 4 (DPPIV)-resistant GLP-1 sequence (GLP-1(7-36;A8G)-NH), were modified with an alkyne (4-pentynoic acid or propiolic acid). These analogs were characterized with respect to human GLP-1 receptor (hGLP-1R) agonist activity, effects on cell viability and human serum stability, revealing that these modifications maintained low (N-terminal; EC 1. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00291DOI Listing

Investigational Therapies for Primary Hyperoxaluria.

Bioconjug Chem 2020 Jun 29. Epub 2020 Jun 29.

Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.

Recent years have brought exciting new insights in the field of primary hyperoxaluria (PH), both on a basic research level as well as through the progress of novel therapeutics in clinical development. To date, very few supportive measures are available for patients suffering from PH, which, together with the severity of the disorder, make disease management challenging. Basic and clinical research and development efforts range from correcting the underlying gene mutations, preventing calcium oxalate crystal-induced kidney damage, to the administration of probiotics favoring the intestinal secretion of excess oxalate. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00268DOI Listing

Nanoparticle-Based Wound Dressing: Recent Progress in the Detection and Therapy of Bacterial Infections.

Bioconjug Chem 2020 Jul 2. Epub 2020 Jul 2.

Cixi Institute of Biomedical Engineering, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, the People's Republic of China.

Bacterial infections in wounds often delay the healing process, and may seriously threaten human life. It is urgent to develop wound dressings to effectively detect and treat bacterial infections. Nanoparticles have been extensively used in wound dressings because of their specific properties. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00297DOI Listing

β-Galactosidase-Catalyzed Fluorescent Reporter Labeling of Living Cells for Sensitive Detection of Cell Surface Antigens.

Bioconjug Chem 2020 Jun 15. Epub 2020 Jun 15.

Dojindo Laboratories, 2025-5 Tabaru, Mashiki-machi, Kumamoto 861-2202, Japan.

The ability to detect cell surface proteins using fluorescent-dye-labeled antibodies is crucial for the reliable identification of many cell types. However, the different types of cell surface proteins used to identify cells are currently limited in number because they need to be expressed at high levels to exceed background cellular autofluorescence, especially in the shorter-wavelength region. Herein we report on a new method, quinone methide-based catalyzed labeling for signal amplification (CLAMP), in which the fluorescence signal is amplified by an enzymatic reaction that strongly facilitates the detection of cell surface proteins on living cells. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00180DOI Listing

Heptamethine Cyanine Dye Mediated Drug Delivery: Hype or Hope.

Bioconjug Chem 2020 Jun 24. Epub 2020 Jun 24.

Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

This review covers the application of heptamethine cyanine dye (HMCD) mediated drug delivery. A relatively small number of HMCDs possess tumor targeting abilities, and this has spurred interest from research groups to explore them as drug delivery systems. Their tumor selectivity is primarily attributed to their uptake by certain isoforms of organic anion transporting polypeptides (OATPs) which are overexpressed in cancer tissues, although there are other possible mechanisms for the observed selectivity still under investigation. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00302DOI Listing

Development of a Versatile and Modular Linker for Antibody-Drug Conjugates Based on Oligonucleotide Strand Pairing.

Bioconjug Chem 2020 Jun 25. Epub 2020 Jun 25.

Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.

Linker design is crucial to the success of antibody-drug conjugates (ADCs). In this work, we developed a modular linker format for attaching molecular cargos to antibodies based on strand pairing between complementary oligonucleotides. We prepared antibody-oligonucleotide conjugates (AOCs) by attaching 18-mer oligonucleotides to an anti-HER2 antibody through thiol-maleimide chemistry, a method generally applicable to any immunoglobulin with interchain disulfide bridges. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00281DOI Listing

Combinatorial Library of Cyclic Benzylidene Acetal-Containing pH-Responsive Lipidoid Nanoparticles for Intracellular mRNA Delivery.

Bioconjug Chem 2020 Jun 24. Epub 2020 Jun 24.

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States.

Lipidoid nanoparticles have been demonstrated to be effective for intracellular delivery of small molecule drugs, proteins, and nucleic acids. Stimuli-responsive lipidoid nanoparticles are able to further improve delivery efficacy and reduce carrier-induced toxicity. Our group previously developed reduction and photoresponsive combinatorial libraries of lipidoid nanoparticles for small molecule and biologics delivery. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00295DOI Listing

A Peptide-Duocarmycin Conjugate Targeting the Thomsen-Friedenreich Antigen Has Potent and Selective Antitumor Activity.

Bioconjug Chem 2020 Jun 15. Epub 2020 Jun 15.

School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR47TJ, United Kingdom.

Solid-phase synthesis allowed the rapid generation of a peptide-drug conjugate. A peptide targeting the Thomsen-Friedenreich antigen (TFα) was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The compound, containing a cathepsin B cleavable linker, was shown to be active and selective against TFα expressing tumor cell lines. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00282DOI Listing

Impact of Ligand Size and Conjugation Chemistry on the Performance of Universal Chimeric Antigen Receptor T-Cells for Tumor Killing.

Bioconjug Chem 2020 Jun 23. Epub 2020 Jun 23.

Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), 8093 Zurich, Switzerland.

All Universal Chimeric Antigen Receptor T-cells (UniCAR T-cells) are T-cells which have been engineered to recognize a haptenated ligand. Due to this feature, UniCAR T-cells have the potential to mediate a potent and selective tumor killing only in the presence of a haptenated tumor ligand, thus avoiding the long-lasting biocidal effects of conventional CAR T-cells. We have used fluorescein-labeled versions of small organic ligands and different antibody formats specific to carbonic anhydrase IX (a tumor-associated antigen) in order to assess whether the killing potential of UniCAR T-cells depended on the molecular features of the haptenated molecule. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00258DOI Listing

Conditionally Controlling Human TLR2 Activity via Trans-Cyclooctene Caged Ligands.

Bioconjug Chem 2020 Jun 8;31(6):1685-1692. Epub 2020 Jun 8.

Department of Bio-Organic Synthesis, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, Zuid-Holland, The Netherlands.

Toll-like receptors (TLRs) are key pathogen sensors of the immune system. Their activation results in the production of cytokines, chemokines, and costimulatory molecules that are crucial for innate and adaptive immune responses. In recent years, specific (sub)-cellular location and timing of TLR activation have emerged as parameters for defining the signaling outcome and magnitude. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303972PMC

Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic Control.

Bioconjug Chem 2020 Jun 19. Epub 2020 Jun 19.

Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.

Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent fashion and has the potential to facilitate weight control. However, native GLP-1 is a short incretin peptide that is susceptible to fast proteolytic inactivation and rapid clearance from the circulation. Various GLP-1 analogs and bioconjugation of GLP-1 analogs have been developed to counter these issues, but these modifications are frequently accompanied by the sacrifice of potency and the induction of immunogenicity. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00286DOI Listing

Large-Scale 3D Optical Mapping and Quantitative Analysis of Nanoparticle Distribution in Tumor Vascular Microenvironment.

Bioconjug Chem 2020 Jun 15. Epub 2020 Jun 15.

Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, South Korea.

Nanoparticles (NPs) are a promising carrier for cancer therapeutics. Systemically administered NPs are transported to tumor tissues via the bloodstream, extravasated from microvessels, and delivered to cancer cells. The distribution of NPs in the tumor vascular microenvironment critically determines the therapeutic efficacy of NP-delivered drugs, but its precise assessment in 3D across a large volume remains challenging. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00263DOI Listing

Tetrazine-TCO Ligation: A Potential Simple Approach to Improve Tumor Uptake through Enhanced Blood Circulation.

Bioconjug Chem 2020 Jun 19. Epub 2020 Jun 19.

Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States.

Targeted imaging via peptides has been extensively investigated for both diagnostic and therapeutic applications. However, peptides can be cleared out from the blood circulation quickly, leading to only moderate to low accumulation in regions of interest. Previously, F-sTCO-DiPhTz-RGDyK demonstrated relatively high blood retention with increased tumor uptake at the late time point (5. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00264DOI Listing

Hyaluronic Acid-Modified Au-Ag Alloy Nanoparticles for Radiation/Nanozyme/Ag Multimodal Synergistically Enhanced Cancer Therapy.

Bioconjug Chem 2020 Jun 11. Epub 2020 Jun 11.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

Gold nanoparticles (AuNPs) have been widely documented as tumor radiosensitizers via enhanced energy deposition of ionizing radiation. However, the sensitization efficiency of AuNPs is still far from satisfactory owing to the irradiation on nontarget tissues and the tumor radio-resistance. To address these issues, we report herein the rational design and development of hyaluronic acid-modified Au-Ag alloy nanoparticles (Au-Ag@HA NPs) with effective tumor radiosensitization by receptor mediated tumor targeting as well as microenvironment-activated hydroxyl radicals (•OH) generation. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00224DOI Listing

Aptamer Enables Consistent Maytansine Delivery through Maintaining Receptor Homeostasis for HER2 Targeted Cancer Therapy.

Bioconjug Chem 2020 Jun 15. Epub 2020 Jun 15.

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, People's Republic of China.

Although the extensive clinical use of the ADC trastuzumab-DM1(T-DM1) for human epidermal growth factor receptor 2 (HER2) targeted cancer therapy, many patients who initially respond to T-DM1 treatment eventually met the insufficient efficacy issue, which is partly attributed to the decreased amount of surface HER2 caused by HER2 degradation in target cells. In our study, we have engineered a HER2 targeted DNA aptamer-DM1 conjugate (HApDC) that can maintain the homeostasis of surface HER2 on the target cancer cell. These conclusions are supported by determining the efficient internalization of HApDC into HER2 overexpressed BT474 and SKBR3 cancer cell lines and by identifying the membranal HER2 level on HApDC-treated BT474 cells. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00250DOI Listing
June 2020
4.513 Impact Factor

Bioinspired Fabrication of Calcium-Doped TiP Coating with Nanofibrous Microstructure to Accelerate Osseointegration.

Bioconjug Chem 2020 Jun 3;31(6):1641-1650. Epub 2020 Jun 3.

Analytical & Testing Center, Sichuan University, Chengdu 610065, China.

Bioinspired by the morphology of osteoclast-resorbed bone surfaces, we prepared a calcium-doped titanium phosphate (Ca-TiP) coating, which consists of a nanofibrous network, on titanium (Ti) substrate via a simple two-step hydrothermal method, trying to mimic natural bone compositionally and microstructurally. The studies show that the Ca-TiP coating with synergistic features of nanofibrous biomimetic topography and surface chemistry could elicit intensively osteogenic behavior and responses including enhanced cell adhesion, spreading, and proliferation as well as alkaline phosphatase (ALP) activity and up-regulated expression of bone-related genes, which inevitably benefit the formation of new bone and the quality of osseointegration. When the two control groups are compared , the significantly improved new bone formation in the early stage and the much stronger interfacial bonding with the surrounding bone for Ca-TiP coating suggest that Ca-TiP coating modified Ti implants hold great potential for orthopedic and dental applications. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00201DOI Listing

Long-Acting Human Growth Hormone Receptor Antagonists Produced in and Conjugated with Polyethylene Glycol.

Bioconjug Chem 2020 Jun 4;31(6):1651-1660. Epub 2020 Jun 4.

Liggins Institute, University of Auckland, Auckland 1023, New Zealand.

Growth hormone (GH) is a peptide hormone that mediates actions through binding to a cell surface GH receptor (GHR). The GHR antagonist, B2036, combines an amino acid substitution at 120 that confers GHR antagonist activity, with eight additional amino acid substitutions. Conjugation to polyethylene glycol (PEG) increases the serum half-life of these proteins due to reduced renal clearance. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00208DOI Listing

Fluorescent Peptide Dendrimers for siRNA Transfection: Tracking pH Responsive Aggregation, siRNA Binding, and Cell Penetration.

Bioconjug Chem 2020 Jun 2;31(6):1671-1684. Epub 2020 Jun 2.

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.

Transfecting nucleic acids into various cells is a key procedure in biological research also envisioned for therapeutic applications. In our effort to obtain simple reagents that would be readily accessible from commercial building blocks, we recently reported peptide dendrimers as single component siRNA transfection reagents accessible in pure form by solid-phase peptide synthesis. Here, we extend our studies of these dendrimers by identifying analogs bearing a coumarin or BODIPY fluorescent label in their core and displaying comparable siRNA transfection efficiencies, pH dependent aggregation, siRNA binding, and secondary structures. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00231DOI Listing

Kinetics and Optimization of the Lysine-Isopeptide Bond Forming Sortase Enzyme from .

Bioconjug Chem 2020 Jun 27;31(6):1624-1634. Epub 2020 May 27.

Site-specifically modified protein bioconjugates have important applications in biology, chemistry, and medicine. Functionalizing specific protein side chains with enzymes using mild reaction conditions is of significant interest, but remains challenging. Recently, the lysine-isopeptide bond forming activity of the sortase enzyme that builds surface pili in (SrtA) has been reconstituted . Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00163DOI Listing

Fully Automated Protein Proximity Assay in Formalin-Fixed, Paraffin-Embedded Tissue Using Caged Haptens.

Bioconjug Chem 2020 Jun 26;31(6):1635-1640. Epub 2020 May 26.

Tissue Research & Early Development, Roche Tissue Diagnostics, Tucson, Arizona 85755, United States.

The ability to interrogate for the presence and distribution of protein-protein complexes (PPCs) is of high importance for the advancement of diagnostic capabilities such as determining therapeutic effects in the context of pharmaceutical development. Herein, we report a novel assay for detecting and visualizing PPCs on formalin-fixed, paraffin-embedded material using a caged hapten. To this end, we synthetically modified a nitropyrazole hapten with an alkaline phosphatase (AP)-responsive self-immolative caging group. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00193DOI Listing

Copper-Doped Nanoscale Covalent Organic Polymer for Augmented Photo/Chemodynamic Synergistic Therapy and Immunotherapy.

Bioconjug Chem 2020 Jun 26;31(6):1661-1670. Epub 2020 May 26.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, P. R. China.

Due to the specific tumor microenvironment (TME) and immunosuppressive state of cancer cells, conventional antitumor therapies face severe challenges, such as high rates of recurrence and metastasis. Herein, Cu-PPT nanoparticles were synthesized based on copper acetate, -phenylenediamine, and 5,10,15,20-tetra-(4-aminophenyl)porphyrin via oxidative coupling reaction for the first time, and the resultant product was used for synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The polymer nanoparticles exhibited excellent photodynamic and photothermal effect with a photothermal conversion efficacy of 40. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00209DOI Listing

Fluorescent Labeling of Proteins of Interest in Live Cells: Beyond Fluorescent Proteins.

Bioconjug Chem 2020 Jun 19;31(6):1587-1595. Epub 2020 May 19.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.

Live cell imaging brings us into a new era of direct visualization of biological processes and molecular dynamics in real time. To visualize dynamic cellular processes and virus-host interactions, fluorescent labeling of proteins of interest is often necessary. Fluorescent proteins are widely used for protein imaging, but they have some intrinsic deficiencies such as big size, photobleaching, and spectrum restriction. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00181DOI Listing

Synthesis and Evaluation of New Trivalent Ligands for Hepatocyte Targeting via the Asialoglycoprotein Receptor.

Bioconjug Chem 2020 May 9;31(5):1313-1319. Epub 2020 May 9.

Chemistry Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation.

Since the asialoglycoprotein receptor (also known as the "Ashwell-Morell receptor" or ASGPR) was discovered as the first cellular mammalian lectin, numerous drug delivery systems have been developed and several gene delivery systems associated with multivalent ligands for liver disease targeting are undergoing clinical trials. The success of these systems has facilitated the further study of new ligands with comparable or higher affinity and less synthetic complexity. Herein, we designed two novel trivalent ligands based on the esterification of tris(hydroxymethyl) aminomethane (TRIS) followed by the azide-alkyne Huisgen cycloaddition with azido -acetyl-d-galactosamine. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00202DOI Listing

Enhancing the Carboxylation Efficiency of Silk Fibroin through the Disruption of Noncovalent Interactions.

Bioconjug Chem 2020 May 8;31(5):1307-1312. Epub 2020 May 8.

Polymer Program, Institute of Materials Science, University of Connecticut, 97 North Eagleville Road Unit 3136, Storrs, Connecticut 06269-3136, United States.

Silk fibroin is a semicrystalline protein used as a renewable polymer source and as a biomaterial platform, but existing methods to synthetically modify fibroin suffer from low efficiencies that can limit the protein's utility. This work reports on a mild synthesis that results in a 2-fold increase in carboxylation through the disruption of noncovalent interactions during the reaction. Importantly, silk fibroin maintains its ability to form β-sheets that are critical for tailoring mechanical and degradation properties, as well as for rendering solid constructs (e. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00168DOI Listing

An Artificial Amphiphilic Peptide Promotes Endocytic Uptake by Inducing Membrane Curvature.

Bioconjug Chem 2020 Jun 13;31(6):1611-1615. Epub 2020 May 13.

Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.

Membrane curvature plays a pivotal role in cellular life, including cellular uptake and membrane trafficking. The modulation of membrane curvature provides a novel means of manipulating cellular events. In this report, we show that a nine-residue amphiphilic peptide (R6W3) stimulates endocytic uptake by inducing membrane curvature. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00239DOI Listing

Precise Installation of Diazo-Tagged Side-Chains on Proteins to Enable In Vitro and In-Cell Site-Specific Labeling.

Bioconjug Chem 2020 Jun 19;31(6):1604-1610. Epub 2020 May 19.

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.

The chemistry of diazo compounds has generated a huge breadth of applications in the field of organic synthesis. Their versatility combined with their tunable reactivity, stability, and chemoselectivity makes diazo compounds desirable reagents for chemical biologists. Here, we describe a method for the precise installation of diazo handles on proteins and antibodies in a mild and specific approach. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00232DOI Listing

Conjugated Protein Domains as Engineered Scaffold Proteins.

Bioconjug Chem 2020 Jun 20;31(6):1596-1603. Epub 2020 May 20.

Laboratory of Chemical Biology, Department of Biomedical Engineering, and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.

Assembly of proteins into higher-order complexes generates specificity and selectivity in cellular signaling. Signaling complex formation is facilitated by scaffold proteins that use modular scaffolding domains, which recruit specific pathway enzymes. Multimerization and recombination of these conjugated native domains allows the generation of libraries of engineered multidomain scaffold proteins. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303964PMC

In Situ One-Step Fluorescence Labeling Strategy of Exosomes via Bioorthogonal Click Chemistry for Real-Time Exosome Tracking In Vitro and In Vivo.

Bioconjug Chem 2020 May 11;31(5):1562-1574. Epub 2020 May 11.

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.

Exosomes are cellular components with promising uses in cancer diagnostics and therapeutics, and their imaging and tracking are essential to study their biological properties. Herein, we report on an in situ one-step fluorescence labeling strategy for exosomes via bioorthogonal click chemistry. First, exosome donor cancer cells were treated with tetraacetylated -azidoacetyl-d-mannosamine (AcManNAz) to generate unnatural azide groups (-N) on their surface via metabolic glycoengineering. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00216DOI Listing
May 2020
4.513 Impact Factor

Cancer Photothermal Therapy with ICG-Conjugated Gold Nanoclusters.

Bioconjug Chem 2020 May 11;31(5):1522-1528. Epub 2020 May 11.

Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, United States.

The coming era of precision nanomedicine demands engineered nanoparticles that can be readily translated into the clinic, like that of molecular agents, without being hindered by intrinsic size heterogeneity and long-term body retention. Herein we report that conjugation of indocyanine green (ICG), an FDA-approved near-infrared (NIR) dye, onto an atomically precise glutathione-coated Au25 (GS-Au25) nanocluster led to a molecular-like photothermal nanoparticle (ICG-GS-Au25) with significantly enhanced ICG photostability and tumor targeting. Under weak NIR light irradiation conditions, free ICG failed to suppress tumor growth but the original tumors were completely eradicated with ICG-GS-Au25. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00172DOI Listing

Installation of a Thermoswitchable Hydrophobic Domain into a Unimer Polyion Complex for Enhanced Cellular Uptake of siRNA.

Bioconjug Chem 2020 May 3;31(5):1320-1326. Epub 2020 May 3.

Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Whereas small siRNA nanocarriers with a size of 10-20 nm exert high tissue-permeability, they encounter the challenge of inefficient adsorption on the cell surface, resulting in poor cellular uptake of siRNA. To solve this dilemma, this study aims to control the hydrophobicity of a small siRNA nanocarrier, unimer polyion complex (uPIC), with a size of ∼10 nm. The uPICs are fabricated to consist of a single pair between siRNA and a smart triblock copolymer comprising hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx), thermoswitchable poly(2--propyl-2-oxazoline) (PnPrOx), and cationic poly(l-lysine) (PLL). Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00238DOI Listing

An Integrin Alpha 6-Targeted Radiotracer with Improved Receptor Binding Affinity and Tumor Uptake.

Bioconjug Chem 2020 May 7;31(5):1510-1521. Epub 2020 May 7.

Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.

In this study, we reported a Tc-labeled integrin α-targeted peptide as the molecular imaging probe for tumor imaging by single-photon emission computed tomography (SPECT). We found that replacing Cys-Cys cyclized RWY peptide (sequence: cCRWYDENAC) with lactam-bridged cyclic cKiE peptide (sequence: cKRWYDENAisoE) did not sacrifice the integrin α-binding affinity and specificity of cKiE radiotracer. To further improve the radiotracer's tumor targeting capability, the dimerized cKiE peptide (termed cKiE2) was designed, and the corresponding radiotracer Tc-cKiE2 was evaluated for tumor uptake and in vivo pharmacokinetics properties in tumor models. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00170DOI Listing

Supramolecular Encapsulation of Small-Ultrared Fluorescent Proteins in Virus-Like Nanoparticles for Noninvasive In Vivo Imaging Agents.

Bioconjug Chem 2020 May 7;31(5):1529-1536. Epub 2020 May 7.

Icosahedral virus-like particles (VLPs) derived from bacteriophages Qβ and PP7 encapsulating small-ultrared fluorescent protein (smURFP) were produced using a versatile supramolecular capsid disassemble-reassemble approach. The generated fluorescent VLPs display identical structural properties to their nonfluorescent analogs. Encapsulated smURFP shows indistinguishable photochemical properties to its unencapsulated counterpart, exhibits outstanding stability toward pH, and produces bright in vitro images following phagocytosis by macrophages. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00190DOI Listing

Compact, "Clickable" Quantum Dots Photoligated with Multifunctional Zwitterionic Polymers for Immunofluorescence and Imaging.

Bioconjug Chem 2020 May 11;31(5):1497-1509. Epub 2020 May 11.

Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, Florida 32306, United States.

We detail the preparation of highly fluorescent quantum dots (QDs), surface-engineered with multifunctional polymer ligands that are compact and readily compatible with strain-promoted click conjugation, and the use of these nanocrystals in immunofluorescence and imaging. The ligand design combines the benefits of mixed coordination (i.e. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00169DOI Listing

Artificial Molecular Chaperone Systems for Proteins, Nucleic Acids, and Synthetic Molecules.

Bioconjug Chem 2020 May 26;31(5):1259-1267. Epub 2020 Apr 26.

Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

Molecular chaperones play critical roles in biological functions. They are closely involved in the maintenance of cell homeostasis, proper folding of proteins and nucleic acids, and inhibition of irreversible aggregation in denatured proteins. In addition to protein production, molecular chaperone function is widely recognized as important for peptide and protein drug delivery systems. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00133DOI Listing

Covalently Immobilizing Interferon-γ Drives Filopodia Production through Specific Receptor-Ligand Interactions Independently of Canonical Downstream Signaling.

Bioconjug Chem 2020 May 11;31(5):1362-1369. Epub 2020 May 11.

Department of Chemistry, The University of Akron, 190 Buchtel Common, Akron, Ohio 44325, United States.

Immobilizing a signaling protein to guide cell behavior has been employed in a wide variety of studies. This approach draws inspiration from biology, where specific, affinity-based interactions between membrane receptors and immobilized proteins in the extracellular matrix guide many developmental and homeostatic processes. Synthetic immobilization approaches, however, do not necessarily recapitulate the signaling system and potentially lead to artificial receptor-ligand interactions. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00105DOI Listing

The Protein Corona Does Not Influence Receptor-Mediated Targeting of Virus-like Particles.

Bioconjug Chem 2020 May 8;31(5):1575-1585. Epub 2020 May 8.

Department of Genetics and Microbiology, Faculty of Science, Charles University, Viničná 5, 128 44 Prague 2, Czech Republic.

Protein corona formation has been regarded as an obstacle to developing diagnostic and therapeutic nanoparticles for applications. Serum proteins that assemble around nanoparticles can hinder their targeting efficiency. Virus-based nanoparticles should be naturally predisposed to evade such barriers in host organisms. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00240DOI Listing

Efficient Sortase-Mediated Ligation Using a Common C-Terminal Fusion Tag.

Bioconjug Chem 2020 May 23;31(5):1463-1473. Epub 2020 Apr 23.

Department of Chemistry, Western Washington University, 516 High Street, Bellingham, Washington 98225, United States.

Sortase-mediated ligation is a powerful method for generating site-specifically modified proteins. However, this process is limited by the inherent reversibility of the ligation reaction. To address this, here we report the continued development and optimization of an experimentally facile strategy for blocking reaction reversibility. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00156DOI Listing

Introduction of an Aldehyde Handle on Nanobodies by Affinity-Guided Labeling.

Bioconjug Chem 2020 May 29;31(5):1295-1300. Epub 2020 Apr 29.

Center for Multifunctional Biomolecular Drug Design at the Interdisciplinary Nanoscience Center, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.

Chemically modified antigen-binding proteins are widely applied for their targeting abilities in the fields of biotechnology, medicine, and diagnostics. However, the production of site-selectively modified proteins remains a challenge. Here, we have designed a chemical probe for the introduction of a reactive aldehyde on nanobodies by metal-complex-guided conjugation. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00151DOI Listing

Metal-Based Nanocatalyst for Combined Cancer Therapeutics.

Bioconjug Chem 2020 May 6;31(5):1247-1258. Epub 2020 May 6.

College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Hebei University, Baoding 071002, P. R. China.

As a classical nanocatalyst-based therapeutic modality, chemodynamic therapy (CDT) has received more and more attention. To improve the therapeutic efficacy of CDT, various metal-based nanocatalysts have been designed and constructed to catalyze the Fenton or Fenton-like reaction in the past few years. However, the therapeutic efficacy of certain CDT is still restricted by the tumor microenvironment, such as limited concentration of intracellular HO, inappropriate pH condition, as well as overexpressed glutathione (GSH). Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00194DOI Listing

Human Granulocyte-Macrophage Colony-Stimulating Factor Fused to Elastin-Like Polypeptides Assembles Biologically-Active Nanoparticles.

Bioconjug Chem 2020 May 5;31(5):1551-1561. Epub 2020 May 5.

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, United States.

Human granulocyte-macrophage colony-stimulating factor (hGMCSF) is crucial in the immune system as it stimulates survival, proliferation, differentiation, and functional activation of myeloid hematopoietic cells. hGMCSF is integral to approved therapies, including monoclonal antibodies against checkpoint inhibitors, chimeric antigen receptors, and prevention of chemotherapy-induced neutropenia. Recombinant hGMCSF can be purified from ; however, it forms inclusion bodies that require solubilization and refolding. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00204DOI Listing

Pyrocinchonimides Conjugate to Amine Groups on Proteins via Imide Transfer.

Bioconjug Chem 2020 May 30;31(5):1449-1462. Epub 2020 Apr 30.

Department of Chemistry, University of California, Irvine, Irvine, California 92697, United States.

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00143DOI Listing
May 2020
4.513 Impact Factor

Recent Advances in Nanomaterials with Inherent Optical and Magnetic Properties for Bioimaging and Imaging-Guided Nucleic Acid Therapy.

Bioconjug Chem 2020 May 30;31(5):1234-1246. Epub 2020 Apr 30.

CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Nucleic acid therapy is and will continue to be of great interest in cancer treatment. The development of nanocarriers with high nucleic acid loading capacity, low toxicity, and specific targeting, with excellent pharmacokinetic/pharmacodynamic profiles, will enable us to realize safe and effective nucleic acid therapy. Tremendous efforts have been directed toward the production of optimized theranostic nanocarriers that can simultaneously provide treatment and real-time monitoring to aid researchers and physicians in making adaptation strategies during early drug development and patient's treatment, respectively. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00126DOI Listing
May 2020
4.513 Impact Factor

Directing Quinone Methide-Dependent Alkylation and Cross-Linking of Nucleic Acids with Quaternary Amines.

Bioconjug Chem 2020 May 23;31(5):1486-1496. Epub 2020 Apr 23.

Polyamine and polyammonium ion conjugates are often used to direct reagents to nucleic acids based on their strong electrostatic attraction to the phosphoribose backbone. Such nonspecific interactions do not typically alter the specificity of the attached reagent, but polyammonium ions dramatically redirected the specificity of a series of quinone methide precursors. Replacement of a relatively nonspecific intercalator based on acridine with a series of polyammonium ions resulted in a surprising change of DNA products. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.0c00166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242154PMC