5,919 results match your criteria Bioconjugate Chemistry [Journal]


Designed synthesis of dual emitting silicon quantum dot for cell imaging: Direct labeling of Alpha 2-HS-Glycoprotein.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

The innocent silicon quantum dots (SQDs) having dual emissive property (blue in VIS and red in NIR), high photo stability and free from auto fluorescence are designed and synthesized for the first time using ethylene glycol. A new attempt has been made for direct labeling of Alpha 2-HS-Glycoprotein (Fetuin A) through functionalizing of the synthesized dots by EDC coupling. The SQDs were characterized by FTIR, TEM, AFM, XRD, EDX, DLS and TGA. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00279DOI Listing

Functionally Versatile and Highly Stable Chelator for 111In and 177Lu: Proof-of-principle Prostate Specific Membrane Antigen Targeting.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Here, we present the synthesis and characterization of a new potentially nonadentate chelator, H4pypa and its bifunctional analog tBu4pypa-C7-NHS conjugated to PSMA (prostate-specific membrane antigen) - targeting peptidomimetic (Glu-urea-Lys). H4pypa is very functionally versatile and biologically stable. Compared to the conventional chelators (e. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00225
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00225DOI Listing
April 2019
1 Read

Trafficking of a Single Photosensitizing molecule to Different Intracellular Organelles Demonstrates Effective Hydroxyl Radical-Mediated Photodynamic Therapy in the Endoplasmic Reticulum.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Photodynamic therapy (PDT) is often used in preclinical and clinical treatment regimens. Reactive oxygen species (ROS) generated by photosensitizers (PSs) upon exposure to light induce cell death via diverse mechanisms. PSs can exert therapeutic effects in different cellular organelles, although the efficacy of organelle-specific PDT has yet to be determined as most previous studies use different PSs in different organelles. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00192DOI Listing

Differential Recognition of Diet-Derived Neu5Gc-Neoantigens on Glycan Microarrays by Carbohydrate-Specific Pooled Human IgG and IgA Antibodies.

Bioconjug Chem 2019 Apr 24. Epub 2019 Apr 24.

The George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology , Tel Aviv University , Tel Aviv 69978 , Israel.

Sialic acids (Sias) cover vertebrate cell surface glycans. N-Acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc) are common Sia in mammals. Humans cannot synthesize Neu5Gc but accumulate it on cells through red-meat rich diets, generating numerous immunogenic Neu5Gc-neoantigens. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00273DOI Listing
April 2019
1 Read

2019 Editorial.

Authors:
Vince Rotello

Bioconjug Chem 2019 Jan;30(1)

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http://dx.doi.org/10.1021/acs.bioconjchem.8b00923DOI Listing
January 2019

Acquired Removability of Aspartic Protease Inhibitors by Direct Biotinylation.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Institute for Quantum Life Science , National Institutes for Quantum and Radiological Science and Technology , Tokai, Ibaraki , 319-1106 , Japan.

Protease inhibitors are used as both research tools and therapeutics. Many of these inhibitors consist of substrate amino acid sequence-derived structure with a transition state mimic to interact with the active site of the protease, suppressing enzymatic activity. However, once they bind, macrodilution or protein denaturation is required to remove them, limiting their usage. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00195
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00195DOI Listing
April 2019
2 Reads

Dextran-Conjugated Caged siRNA Nanoparticles for Photochemical Regulation of RNAi-Induced Gene Silencing in Cells and Mice.

Bioconjug Chem 2019 Apr 24. Epub 2019 Apr 24.

State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences , Peking University , Beijing , 100191 , China.

RNA interference (RNAi)-based gene therapy is a precision therapeutic approach for highly efficient sequence-specific gene silencing in vivo or in vitro. Caged RNAs featuring dextran conjugation of antisense and sense RNA strands using photolabile linker were rationally designed and self-assembled to form caged siRNA nanoparticles (Dex- p-siRNA) for photoregulation of target gene expression. The dextran-conjugated caged siRNA nanoparticles showed significant serum nuclease-resistance due to the formation of dextran-siRNA nanoparticles. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00204DOI Listing

Antigen Engineering Approaches for Lyme Disease Vaccines.

Bioconjug Chem 2019 Apr 24. Epub 2019 Apr 24.

Department of Biomedical Engineering , University at Buffalo, State University of New York , Buffalo , New York 14260 , United States.

Increasing rates of Lyme disease necessitate preventive measures such as immunization to mitigate the risk of contracting the disease. At present, there is no human Lyme disease vaccine available on the market. Since the withdrawal of the first and only licensed Lyme disease vaccine based on lipidated recombinant OspA, vaccine and antigen research has aimed to overcome its risks and shortcomings. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00167DOI Listing
April 2019
1 Read

Screening, Identification, and Characterization of an Affinity Peptide Specific to MT1-MMP and Its Application in Tumor Imaging.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Key Laboratory of Molecular Enzymology and Enzyme Engineering of the Ministry of Education , Jilin University , 2699 Qianjin Street , Changchun 130012 , P. R. China.

Membrane type-1 matrix metalloproteinase (MT1-MMP) plays a crucial role in many physiological and pathological processes, especially in tumor invasion and metastasis. Bioimaging of this key molecule may find wide usage in various applications. MT-loop is a unique sequence of MT1-MMP and locates in the surface of the protein. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00220DOI Listing

Molecular Tools to Generate Reactive Oxygen Species in Biological Systems.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, Department of Chemistry, and the UVA Cancer Center , University of Virginia , 1340 Jefferson Park Avenue , Charlottesville , Virginia 22908 , United States.

Reactive oxygen species (ROS) not only are byproducts of aerobic respiration, but also play vital roles in metabolism regulation and signal transductions. It is important to understand the functions of ROS in biological systems. In addition, scientists have made use of ROS to kill bacteria and tumors through a process known as photodynamic therapy (PDT). Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00191
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00191DOI Listing
April 2019
1 Read

Directed Energy Transfer through DNA-Templated J-Aggregates.

Bioconjug Chem 2019 Apr 23. Epub 2019 Apr 23.

Department of Chemistry , National Institute of Technology , Tiruchirappalli 620015 , Tamil Nadu , India.

Strongly coupled molecular dye aggregates have unique optoelectronic properties that often resemble those of light harvesting complexes found in Nature. The exciton dynamics in coupled dye aggregates could enhance the long-range transfer of optical excitation energy with high efficiency. In principle, dye aggregates could serve as important components in molecular-scale photonic devices; however, rational design of these coupled dye aggregates with precise control over their organization, interactions, and dynamics remains a challenge. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00043DOI Listing

Fluorogenic Photoaffinity Labeling of Proteins in Living Cells.

Bioconjug Chem 2019 Apr 17. Epub 2019 Apr 17.

Department of Chemistry , Emory University , Atlanta , Georgia 30322 , United States.

Genetically encoded fluorescent proteins or small-molecule probes that recognize specific protein binding partners can be used to label proteins to study their localization and function with fluorescence microscopy. However, these approaches are limited in signal-to-background resolution and the ability to temporally control labeling. Herein, we describe a covalent protein labeling technique using a fluorogenic malachite green probe functionalized with a photoreactive cross-linker. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00203
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00203DOI Listing
April 2019
1 Read

[F]-SuPAR: A Radiofluorinated Probe for Noninvasive Imaging of DNA Damage-Dependent Poly(ADP-ribose) Polymerase Activity.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Poly(ADP ribose) polymerase (PARP) enzymes generate poly(ADP ribose) post-translational modifications on target proteins for an array of functions centering on DNA and cell stress. PARP isoforms 1 and 2 are critically charged with the surveillance of DNA integrity and are the first line guardians of the genome against DNA breaks. Here we present a novel probe ([F]-SuPAR) for noninvasive imaging of PARP-1/2 activity using positron emission tomography (PET). Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00089DOI Listing
April 2019
1 Read

Noninvasive Imaging and Quantification of Radiotherapy-Induced PD-L1 Upregulation with Zr-Df-Atezolizumab.

Bioconjug Chem 2019 Apr 19. Epub 2019 Apr 19.

Medical Physics Department , University of Wisconsin-Madison , 1111 Highland Avenue , Madison , Wisconsin 53705 , United States.

Immune checkpoint expression is highly dynamic, and combination treatments including radiotherapy can particularly modulate this expression. PET imaging using Zr-Df-atezolizumab can provide insight into the levels of PD-L1 variation following radiotherapy treatments. In vitro screening was used to monitor PD-L1 expression by lung cancer cells following radiotherapy. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00178DOI Listing
April 2019
2 Reads

Development of a NanoBRET-Based Sensitive Screening Method for CXCR4 Ligands.

Bioconjug Chem 2019 Apr 11. Epub 2019 Apr 11.

Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering , Tokyo Medical and Dental University (TMDU) , 2-3-10 Kandasurugada , Chiyoda-ku, Tokyo 101-0062 , Japan.

A critical part of the development of CXCR4 modulators is to have a simple and sensitive assay system to complement the search by screening and evaluating the binding affinity. Herein, a NanoBRET assay system was developed, and its feasibility as a high-throughput screening tool for potent CXCR4 ligands was ascertained. TAMRA-Ac-TZ14011, a fluorescent-labeled CXCR4 antagonist, was adopted as a fluorescent acceptor of bioluminescent energy from N-terminally fused NanoLuc-CXCR4 stably expressed in CHO cells. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00182
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00182DOI Listing
April 2019
4 Reads

Recent Advances in Amphiphilic Polymer-Oligonucleotide Nanomaterials via Living/Controlled Polymerization Technologies.

Bioconjug Chem 2019 Apr 19. Epub 2019 Apr 19.

Departments of Chemistry, Materials Science & Engineering, and Biomedical Engineering, International Institute for Nanotechnology, and Simpson Querrey Institute , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208-3113 , United States.

Over the past decade, the field of polymer-oligonucleotide nanomaterials has flourished because of the development of synthetic techniques, particularly living polymerization technologies, which provide access to polymers with well-defined architectures, precise molecular weights, and terminal or side-chain functionalities. Various "living" polymerization methods have empowered chemists with the ability to prepare functional polymer-oligonucleotide conjugates yielding a library of architectures, including linear diblock, comb, star, hyperbranched star, and gel morphologies. Since oligonucleotides are hydrophilic and synthetic polymers can be tailored with hydrophobicity, these amphiphilic polymer-oligonucleotide conjugates are capable of self-assembling into nanostructures with different shapes, leading to many high-value-added biomedical applications, such as drug delivery systems, gene regulation, and 3D-bioprinting. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00166DOI Listing

Development of a Cross-Reactive Monoclonal Antibody for Detecting the Tumor Stroma.

Bioconjug Chem 2019 Apr 18. Epub 2019 Apr 18.

Department of Pharmacology , University of Minnesota Medical School , Minneapolis , Minnesota 55455 , United States.

Here, we document the discovery of a monoclonal antibody that selectively binds to both human and murine fibroblast activation protein alpha (FAP), a serine protease that is overexpressed on cancer-associated fibroblasts (CAFs), making it an attractive therapeutic target for the aiding and abetting tumor microenvironment. The lead antibody, B12, was identified from a naïve murine single-chain variable fragment antibody phage display library screened against recombinant human FAP on magnetic beads. The heavy and light chains of B12 were cloned into full-length human immunoglobulin 1 (IgG) vectors and expressed as a chimeric monoclonal antibody (B12 IgG). Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00206
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00206DOI Listing
April 2019
5 Reads

Catalytic Mechanisms of Nanozymes and Their Applications in Biomedicine.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

School of Biological Science and Medical Engineering , Southeast University, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices , Nanjing , Jiangsu 210096 , P.R. China.

The research on nanozymes has increased dramatically in recent years and a new interdiscipline, nanozymology, has emerged. A variety of nanomaterials have been designed to mimic the characteristics of natural enzymes, which connects an important bridge between nanotechnology and biological science. Unlike natural enzymes, the nanoscale properties of nanozymes endow them with the potential to regulate their enzymatic-like activity from different perspectives. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00171DOI Listing
April 2019
4.513 Impact Factor

Antibody-Drug Conjugates Derived from Cytotoxic seco-CBI-Dimer Payloads Are Highly Efficacious in Xenograft Models and Form Protein Adducts In Vivo.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Genentech Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.

This work discloses the first examples of antibody-drug conjugates (ADCs) that are constructed from linker-drugs bearing dimeric seco-CBI payloads (duocarmycin analogs). Several homogeneous, CD22-targeting THIOMAB antibody-drug conjugates (TDCs) containing the dimeric seco-CBI entities are shown to be highly efficacious in the WSU-DLCL2 and BJAB mouse xenograft models. Surprisingly, the seco-CBI-containing conjugates are also observed to undergo significant biotransformation in vivo in mice, rats, and monkeys and thereby form 1:1 adducts with the Alpha-1-Microglobulin (A1M) plasma protein from these species. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00133DOI Listing
April 2019
3 Reads

Modification of Serum Albumin by High Conversion of Carboxyl to Amino Groups Creates a Potent Inhibitor of Amyloid β-Protein Fibrillogenesis.

Bioconjug Chem 2019 Apr 16. Epub 2019 Apr 16.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology , Tianjin University , Tianjin 300072 , China.

Fibrillogenesis of amyloid β-protein (Aβ) has been thought to be implicated in the progression of Alzheimer's disease (AD). Therefore, development of high-efficiency inhibitors is one of the strategies for the prevention and treatment of AD. Serum albumin has been found to capture Aβ monomers through its hydrophobic groove and suppress amyloid formation, but the inhibition efficiency is limited. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00209DOI Listing

Multistep Synthesis of 1,2,4-Oxadiazoles via DNA-Conjugated Aryl Nitrile Substrates.

Bioconjug Chem 2019 Apr 10. Epub 2019 Apr 10.

Center for Drug Discovery, Department of Pathology and Immunology , Baylor College of Medicine , Houston , Texas 77030 , United States.

A multistep protocol for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles on DNA-chemical conjugates has been developed. A set of six DNA-connected aryl nitriles were converted to corresponding amidoximes with hydroxylamine followed by the O-acylation with a series of aryl and aliphatic carboxylic acids. After cyclodehydration of the O-acyl amidoximes by heating at 90 °C in pH 9. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00188DOI Listing
April 2019
6 Reads

Penetration and Uptake of Nanoparticles in 3D Tumor Spheroids.

Bioconjug Chem 2019 Apr 12. Epub 2019 Apr 12.

Innovation Strategies and External Liaison, Pharmaceutical Technology and Development , AstraZeneca , Macclesfield , SK10 2NA , United Kingdom.

Animal models are effective for assessing tumor localization of nanosystems but difficult to use for studying penetration beyond the vasculature. Here, we have used well-characterized HCT116 colorectal cancer spheroids to study the effect of nanoparticle (NP) physicochemical properties on penetration and uptake. Incubation of spheroids with Hoechst 33342 resulted in a dye gradient, which facilitated discrimination between the populations of cells in the core and at the periphery of spheroids by flow cytometry. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00136DOI Listing
April 2019
2 Reads

Site-Selective Synthesis of Insulin Azides and Bioconjugates.

Bioconjug Chem 2019 Apr 4;30(4):1127-1132. Epub 2019 Apr 4.

Chemistry Capabilities for Accelerating Therapeutics , Merck & Co., Inc. , Kenilworth , New Jersey 07033 , United States.

A synthetic method to access novel azido-insulin analogs directly from recombinant human insulin (RHI) was developed via diazo-transfer chemistry using imidazole-1-sulfonyl azide. Systematic optimization of reaction conditions led to site-selective azidation of amino acids B1-phenylalanine and B29-lysine present in RHI. Subsequently, the azido-insulin analogs were used in azide-alkyne [3 + 2] cycloaddition reactions to synthesize a diverse array of triazole-based RHI bioconjugates that were found to be potent human insulin receptor binders. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00069
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00069DOI Listing
April 2019
2 Reads
4.513 Impact Factor

Site-Specific Reversible Protein and Peptide Modification: Transglutaminase-Catalyzed Glutamine Conjugation and Bioorthogonal Light-Mediated Removal.

Bioconjug Chem 2019 Apr 15. Epub 2019 Apr 15.

Dynamic photoswitches in proteins that impart spatial and temporal control are important to manipulate and study biotic and abiotic processes. Nonetheless, approaches to install these switches into proteins site-specifically are limited. Herein we describe a novel site-specific method to generate photoremovable protein conjugates. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00145DOI Listing
April 2019
3 Reads

Chondroitin Sulfate-Based pH-Sensitive Polymer-Modified Liposomes for Intracellular Antigen Delivery and Induction of Cancer Immunity.

Bioconjug Chem 2019 Apr 11. Epub 2019 Apr 11.

Department of Applied Chemistry Graduate School of Engineering , Osaka Prefecture University , 1-1 Gakuen-cho , Naka-ku, Sakai , Osaka 599-8531 , Japan.

Induction of cancer-specific cytotoxic T lymphocytes is crucially important to complement therapeutic effects of immune checkpoint inhibitors and to achieve efficient cancer immunotherapy. To induce cancer-specific cytotoxic T lymphocytes, cancer antigen carriers must have multiple functions to deliver cancer antigens to antigen presenting cells, release antigens into cytosol, and promote the maturation of these cells. We earlier achieved cytosolic delivery of antigens and induction of antigen-specific cytotoxic T lymphocytes using carboxylated polyglycidol or polysaccharide derivative-modified liposomes that can induce membrane fusion with endosomes in response to weakly acidic pH. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00221DOI Listing

Extradomain-B Fibronectin-Targeted Dextran-Based Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Probe for Detecting Pancreatic Cancer.

Bioconjug Chem 2019 Apr 15. Epub 2019 Apr 15.

Department of Radiology , Johns Hopkins University , Baltimore , Maryland 21205 , United States.

A dextran-peptide conjugate was developed for magnetic resonance (MR) molecular imaging of pancreatic ductal adenocarcinoma (PDAC) through its overexpressed microenvironment biomarker, extradomain-B fibronectin (EDB-FN). This new agent consists of diamagnetic and biocompatible dextran and a targeting peptide. Dextrans can be directly detected by chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) without the need for radionuclide or metallic labeling. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00161DOI Listing
April 2019
4.513 Impact Factor

Characterization of Antibody Products Obtained through Enzymatic and Nonenzymatic Glycosylation Reactions with a Glycan Oxazoline and Preparation of a Homogeneous Antibody-Drug Conjugate via Fc N-Glycan.

Bioconjug Chem 2019 Apr 17. Epub 2019 Apr 17.

Synthetic Cellular Chemistry Laboratory , RIKEN , Hirosawa, Wako , Saitama , 351-0198 Japan.

Glycan engineering of antibodies has received considerable attention. Although various endo-β- N-acetylglucosaminidase mutants have been developed for glycan remodeling, a side reaction has been reported between glycan oxazoline and amino groups. In this study, we performed a detailed characterization for antibody products obtained through enzymatic and nonenzymatic reactions with the aim of maximizing the efficiency of the glycosylation reaction with fewer side products. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00132
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00132DOI Listing
April 2019
2 Reads

Diverted Natural Lossen-type Rearrangement for Bioconjugation through in Situ Myrosinase-Triggered Isothiocyanate Synthesis.

Bioconjug Chem 2019 Apr 16. Epub 2019 Apr 16.

Normandie Univ , CNRS, UNIROUEN, INSA Rouen, COBRA (UMR 6014) , 76000 Rouen , France.

Fluorescein isothiocyanate (FITC) is one of the most extensively used fluorescent probes for the labeling of biomolecules. The isothiocyanate function reacts with lysine residues of proteins to provide a chemically stable thiourea linkage without releasing any byproduct. However, diversification of isothiocyanate-based reagents is still hampered by the lack of mild conditions to generate isothiocyanate chemical functions, as well as by their poor stability and limited solutions available to increase water solubility, restricting the use of isothiocyanate labeling to highly water-soluble fluorophores. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00153DOI Listing
April 2019
3 Reads

A Near-IR Fluorescent Dasatinib Derivative That Localizes in Cancer Cells.

Bioconjug Chem 2019 Apr 1;30(4):1175-1181. Epub 2019 Apr 1.

Department of Chemistry , Texas A & M University , Box 30012, College Station , Texas 77842 , United States.

Kinase inhibitors (KIs) have had a huge impact on clinical treatment of various cancers, but they are far from perfect medicines. In particular, their efficacies are limited to certain cancer types and, in many cases, provide only temporary remission. This paper explores the possibility of covalently binding a fluorophore for in vivo optical imaging to the KI dasatinib where the particular fluorophore chosen for this study, a heptamethine cyanine (Cy) derivative, tends to accumulate in tumors. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00118DOI Listing
April 2019
1 Read

Red Fluorescence Probe Targeted to Dipeptidylpeptidase-IV for Highly Sensitive Detection of Esophageal Cancer.

Bioconjug Chem 2019 Apr 3;30(4):1055-1060. Epub 2019 Apr 3.

AMED-CREST, Japan Agency for Medical Research and Development , 1-7-1 Otemachi , Chiyoda-ku , Tokyo 100-0004 , Japan.

We have developed an activatable red fluorescence probe for dipeptidylpeptidase-IV (DPP-IV) by precisely controlling the photoinduced electron transfer (PeT) process of a red fluorescent scaffold, SiR600. The developed probe exhibited an extremely low background signal and showed significant fluorescence activation upon reaction with DPP-IV, enabling sensitive detection of esophageal cancer in clinical specimens from cancer patients. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00198DOI Listing

Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake toward Targeted Drug Delivery.

Bioconjug Chem 2019 Apr 5;30(4):1220-1231. Epub 2019 Apr 5.

Molecular and Cellular Biology Program , University of Massachusetts Amherst , Amherst , Massachusetts 01003 , United States.

Conjugation of proteins to drug-loaded polymeric structures is an attractive strategy for facilitating target-specific drug delivery for a variety of clinical needs. Polymers currently available for conjugation to proteins generally have limited chemical versatility for subsequent drug loading. Many polymers that do have chemical functionality useful for drug loading are often insoluble in water, making it difficult to synthesize functional protein-polymer conjugates for targeted drug delivery. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00155DOI Listing
April 2019
1 Read

Improved Inhibition of Tumor Growth by Diabody-Drug Conjugates via Half-Life Extension.

Bioconjug Chem 2019 Apr 3;30(4):1232-1243. Epub 2019 Apr 3.

Spirogen , 42 New Road , E1 2AX , London , United Kingdom.

Despite some clinical success with antibody-drug conjugates (ADCs) in patients with solid tumors and hematological malignancies, improvements in ADC design are still desirable due to the narrow therapeutic window of these compounds. Tumor-targeting antibody fragments have distinct advantages over monoclonal antibodies, including more rapid tumor accumulation and enhanced penetration, but are subject to rapid clearance. Half-life extension technologies such as PEGylation and albumin-binding domains (ABDs) have been widely used to improve the pharmacokinetics of many different types of biologics. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00170DOI Listing
April 2019
4 Reads

Unprecedented Thiacalixarene Fucoclusters as Strong Inhibitors of Ebola cis-Cell Infection and HCMV-gB Glycoprotein/DC-SIGN C-type Lectin Interaction.

Bioconjug Chem 2019 Apr 4;30(4):1114-1126. Epub 2019 Apr 4.

Laboratoire de Glycochimie des Antimicrobiens et des Agroressources (LG2A-UMR7378-CNRS) , Université de Picardie Jules Verne , 10 Rue Baudelocque , 80039 , Amiens , France.

Glycan-protein interactions control numerous biological events from cell-cell recognition and signaling to pathogen host cell attachment for infections. To infect cells, some viruses bind to immune cells with the help of DC-SIGN (dendritic cell [DC]-specific ICAM3-grabbing nonintegrin) C-type lectin expressed on dendritic and macrophage cell membranes, via their envelope protein. Prevention of this infectious interaction is a serious therapeutic option. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00066DOI Listing
April 2019
4 Reads

A Metal-Free DOTA-Conjugated F-Labeled Radiotracer: [F]DOTA-AMBF-LLP2A for Imaging VLA-4 Over-Expression in Murine Melanoma with Improved Tumor Uptake and Greatly Enhanced Renal Clearance.

Bioconjug Chem 2019 Apr 8;30(4):1210-1219. Epub 2019 Apr 8.

Chemistry Department , University of British Columbia , 2036 Main Mall , Vancouver , British Columbia V6T 1Z1 , Canada.

DOTA is commonly used for radiometal chelation in molecular imaging. Yet in the absence of a radiometal, DOTA is hypothesized to promote renal clearance of F-labeled peptide tracers. In light of an increasing interest in the use of F18 for PET, here the effect of DOTA is evaluated for the first time with an F-labeled tracer and is found to significantly improve the quality of images acquired through positron emission tomography (PET). Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00146
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00146DOI Listing
April 2019
1 Read

Development of Mirror-Image Screening Systems for XIAP BIR3 Domain Inhibitors.

Bioconjug Chem 2019 Apr 17. Epub 2019 Apr 17.

Graduate School of Pharmaceutical Sciences , Kyoto University , Sakyo-ku, Kyoto 606-8501 , Japan.

The X-linked inhibitor of apoptosis protein baculovirus IAP repeat (XIAP BIR3) domain is a promising therapeutic target for cancer treatment. For the mirror-image screening campaign to identify drug candidates from an unexplored mirror-image natural product library, a facile synthetic protocol for XIAP BIR3 domain synthesis was established by a native chemical ligation strategy using conserved cysteines present among BIR domains. The native and mirror-image XIAP BIR3 domains with an appropriate functional group for labeling were prepared using the established protocol. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00154DOI Listing

Long-Distance Tracing of the Lymphatic System with a Computed Tomography/Fluorescence Dual-Modality Nanoprobe for Surveying Tumor Lymphatic Metastasis.

Bioconjug Chem 2019 Apr 1;30(4):1199-1209. Epub 2019 Apr 1.

Britton Chance Center for Biomedical Photonics , Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology , Wuhan , Hubei 430074 , China.

Noninvasive visualization of deep tissue lymphatic metastasis is crucial for diagnosing malignant tumors and predicting prognosis. However, the limited diffusivity and specificity of imaging contrast agents that are transported in lymph vessels (LVs), even for those agents delivered by nanocarriers, make long-distance tracing of the lymphatic system in vivo challenging. Here, we develop a computed tomography (CT)/fluorescence dual-modality phospholipid nanoprobe (PL(I/D)NP) with a negative charge and sub-60 nm size. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00144DOI Listing
April 2019
1 Read

Enzymatic and Site-Specific Ligation of Minimal-Size Tetrazines and Triazines to Proteins for Bioconjugation and Live-Cell Imaging.

Bioconjug Chem 2019 Apr 22. Epub 2019 Apr 22.

Institute of Pharmacy and Molecular Biotechnology , Heidelberg University , Im Neuenheimer Feld 364 , 69120 Heidelberg , Germany.

Diels-Alder reactions with inverse electron demand (DA) have emerged as an indispensable tool for bioorthogonal labeling and the manipulation of biomolecules. In this context, reactions between tetrazines and strained dienophiles have received attention because of high reaction rates. Current methods for the DA-mediated functionalization of proteins suffer from slow reactivity, impaired stability, isomerization, or elimination of the incorporated strained dienophiles. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00157DOI Listing
April 2019
1 Read

Semisynthesis of an Active Enzyme by Quantitative Click Ligation.

Bioconjug Chem 2019 Apr 28;30(4):1169-1174. Epub 2019 Mar 28.

Center for Evolutionary Chemical Biology, Department of Chemistry , University of Copenhagen , Universitetsparken 5 , 2100 Copenhagen , Denmark.

The incorporation of clickable noncanonical amino acids (ncAAs) has proven to an invaluable tool in chemical biology and protein science research. Nevertheless, the number of examples in which the method is used for preparative purposes is extremely limited. We report the synthesis of an active enzyme by quantitative, Cu(I)-catalyzed ligation of two inactive protein halves, expressed and equipped with an azide and alkyne moiety, respectively, through ncAA incorporation. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00110DOI Listing
April 2019
1 Read

Trapped! A Critical Evaluation of Methods for Measuring Total Cellular Uptake versus Cytosolic Localization.

Bioconjug Chem 2019 Apr 5;30(4):1006-1027. Epub 2019 Apr 5.

Department of Biochemistry , University of Zurich , Winterthurerstrasse 190 , 8057 Zurich , Switzerland.

Biomolecules have many properties that make them promising for intracellular therapeutic applications, but delivery remains a key challenge because large biomolecules cannot easily enter the cytosol. Furthermore, quantification of total intracellular versus cytosolic concentrations remains demanding, and the determination of delivery efficiency is thus not straightforward. In this review, we discuss strategies for delivering biomolecules into the cytosol and briefly summarize the mechanisms of uptake for these systems. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00112DOI Listing
April 2019
1 Read

Polyvalent Diazonium Polymers Provide Efficient Protection of Oncolytic Adenovirus Enadenotucirev from Neutralizing Antibodies while Maintaining Biological Activity In Vitro and In Vivo.

Bioconjug Chem 2019 Apr 27;30(4):1244-1257. Epub 2019 Mar 27.

School of Pharmacy , University of Nottingham , Nottingham NG7 2RD , U.K.

Oncolytic viruses offer many advantages for cancer therapy when administered directly to confined solid tumors. However, the systemic delivery of these viruses is problematic because of the host immune response, undesired interactions with blood components, and inherent targeting to the liver. Efficacy of systemically administered viruses has been improved by masking viral surface proteins with polymeric materials resulting in modulation of viral pharmacokinetic profile and accumulation in tumors in vivo. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00189
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00189DOI Listing
April 2019
6 Reads

Measuring the Impact of PEGylation on a Protein-Polysaccharide Interaction.

Bioconjug Chem 2019 Apr 21;30(4):1162-1168. Epub 2019 Mar 21.

School of Chemistry , National University of Ireland Galway , University Road , Galway , H91 TK33 , Ireland.

PEGylation is the most widely used half-life extension strategy for protein therapeutics. While it imparts a range of attractive attributes PEGylation can impede protein binding and reduce efficacy. A model system to probe the effects of PEGylation on protein binding has practical applications. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00099DOI Listing

Membrane Scaffolds Enhance the Responsiveness and Stability of DNA-Based Sensing Circuits.

Bioconjug Chem 2019 Mar 29. Epub 2019 Mar 29.

Biological and Soft Systems, Cavendish Laboratory , University of Cambridge , JJ Thomson Avenue , Cambridge CB3 0HE , United Kingdom.

Target-induced DNA strand displacement is an excellent candidate for developing analyte-responsive DNA circuitry to be used in clinical diagnostics and synthetic biology. While most available technologies rely on DNA circuitry free to diffuse in bulk, here we explore the use of liposomes as scaffolds for DNA-based sensing nanodevices. Our proof-of-concept sensing circuit responds to the presence of a model target analyte by releasing a DNA strand, which in turn activates a fluorescent reporter. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00080DOI Listing
March 2019
2 Reads

Dual Synthetic Peptide Conjugate Vaccine Simultaneously Triggers TLR2 and NOD2 and Activates Human Dendritic Cells.

Bioconjug Chem 2019 Apr 26;30(4):1150-1161. Epub 2019 Mar 26.

Leiden Institute of Chemistry , Leiden University , Einsteinweg 55 , 2333 CC Leiden , The Netherlands.

Simultaneous triggering of Toll-like receptors (TLRs) and NOD-like receptors (NLRs) has previously been shown to synergistically activate monocytes, dendritic cells, and macrophages. We applied these properties in a T-cell vaccine setting by conjugating the NOD2-ligand muramyl-dipeptide (MDP) and TLR2-ligand PamCSK to a synthetic peptide derived from a model antigen. Stimulation of human DCs with the MDP-peptide-PamCSK conjugate led to a strongly increased secretion of pro-inflammatory and Th1-type cytokines and chemokines. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00087DOI Listing
April 2019
1 Read

Hybrid Cell-Penetrating Foldamer with Superior Intracellular Delivery Properties and Serum Stability.

Bioconjug Chem 2019 Apr 1;30(4):1133-1139. Epub 2019 Apr 1.

Equipe 3Bio , CAMB 7199 CNRS-Univ. Strasbourg, Faculté de Pharmacie , 74 route du Rhin , F-67401 Illkirch cedex, France.

Sequence specific molecules with high folding ability (i.e., foldamers) can be used to precisely control the distribution and projection of side chains in space and have recently been introduced as tailored systems for delivering nucleic acids into cells. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00075DOI Listing

DNA-Functionalized Supramolecular Polymers: Dynamic Multicomponent Assemblies with Emergent Properties.

Bioconjug Chem 2019 Mar 22. Epub 2019 Mar 22.

Recent years have witnessed an increasing interest in hybrid molecular systems in which the programmability of DNA hybridization is used to introduce enhanced molecular control in synthetic systems. The first examples of DNA-functionalized supramolecular polymers have been reported only recently, but have already revealed structural and functional properties that are not easily obtained in either synthetic supramolecular polymers or DNA-only based systems. In this Topical Review, we provide an overview of the various forms of additional control offered by DNA hybridization for different types of supramolecular polymers and discuss how orthogonal supramolecular interactions in these hybrid systems can give rise to emergent structural and functional properties. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00095DOI Listing

Topological Design of Star Glycopolymers for Controlling the Interaction with the Influenza Virus.

Bioconjug Chem 2019 Apr 20;30(4):1192-1198. Epub 2019 Mar 20.

Department of Chemical Engineering , Kyushu University , 744 Motooka Nishi-ku , Fukuoka 819-0395 , Japan.

The precise design of synthetic polymer ligands using controlled polymerization techniques provides an advantage for the field of nanoscience. We report the topological design of glyco-ligands based on synthetic polymers for targeting hemagglutinin (HA, lectin on the influenza virus). To achieve precise arrangement of the glycounits toward the sugar-binding pockets of HA, triarm star glycopolymers were synthesized. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00134DOI Listing

Functionalization of Clinically Approved MRI Contrast Agents for the Delivery of VEGF.

Bioconjug Chem 2019 Apr 14;30(4):1042-1047. Epub 2019 Mar 14.

Division of Cardiovascular Imaging, Department of Cardiology I , University Hospital Münster , Albert-Schweitzer-Campus 1 , 48149 Münster , Germany.

In combining the two clinically approved substances ferumoxytol and VEGF-165 via peptide coupling, we propose a straightforward approach to obtain a potentially ready-to-use theranostic contrast agent for specific cardiovascular diseases. Clinical and preclinical magnetic resonance imaging (MRI) studies have shown that intravenously applied superparamagnetic ferumoxytol nanoparticles accumulate in acute ischemic myocardial tissue. On the other hand, growth factors such as VEGF-165 (vascular endothelial growth factor) play a major role during angiogenesis and vasculogenesis. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00142DOI Listing

Harnessing Exosomes for the Development of Brain Drug Delivery Systems.

Bioconjug Chem 2019 Apr 21;30(4):994-1005. Epub 2019 Mar 21.

Department of Pharmacology and Chemical Biology , Shanghai Jiao Tong University School of Medicine , Shanghai 200025 , China.

Brain drug delivery is one of the most important bottlenecks in the development of drugs for the central nervous system. Cumulative evidence has emerged that extracellular vesicles (EVs) play a key role in intercellular communication. Exosomes, a subgroup of EVs, have received the most attention due to their capability in mediating the horizontal transfer of their bioactive inclusions to neighboring and distant cells, and thus specifically regulating the physiological and pathological functions of the recipient cells. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00085
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00085DOI Listing
April 2019
7 Reads

Disulfide Modified IgG1: An Investigation of Biophysical Profile and Clinically Relevant Fc Interactions.

Bioconjug Chem 2019 Apr 18;30(4):1048-1054. Epub 2019 Mar 18.

Department of Chemistry , University College London , 20 Gordon Street , WC1H OAJ , London , United Kingdom.

Modification of immunoglobulin G (IgG) 1 proteins in cancer treatment is a rapidly growing field of research. Antibody-drug conjugates (ADCs) exploit the targeted nature of this immunotherapy by conjugating highly potent drugs to antibodies, allowing for effective transport of cargo(s) to cancerous cells. Of the many bioconjugation strategies now available for the formation of highly homogeneous ADCs, disulfide modification is considered an effective, low-cost, and widely accepted method for modifying IgG1s for improved clinical benefit. Read More

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http://pubs.acs.org/doi/10.1021/acs.bioconjchem.9b00174
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00174DOI Listing
April 2019
8 Reads

Characterization and Biodistribution Analysis of Oxygen-Doped Single-Walled Carbon Nanotubes Used as in Vivo Fluorescence Imaging Probes.

Bioconjug Chem 2019 Mar 20. Epub 2019 Mar 20.

School of Life Science and Technology , Tokyo Institute of Technology , 4259 Nagatsuta-cho , Midori-ku, Yokohama , Kanagawa 226-8503 Japan.

Single-walled carbon nanotubes (SWCNTs) show strong fluorescence in the 1000-1700 nm second near-infrared (NIR-II) wavelength range and are considered promising candidates for angiographic imaging probes. Oxygen-doped SWCNTs coated with phospholipid-polyethylene glycol (o-SWCNT-PEG) show exceptional potential, as they emit fluorescence at ∼1300 nm through excitation with 980 nm light. Here, with the aim of putting o-SWCNTs to practical use as an angiographic agent in animal experiments, the retention time after intravenous administration in the vasculature of mice and the biodistribution were studied. Read More

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http://dx.doi.org/10.1021/acs.bioconjchem.9b00088DOI Listing
March 2019
2 Reads