1,220 results match your criteria variable linker

Development of a single-chain fragment variable fused-mutant HALT-1 recombinant immunotoxin against G12V mutated olorectal cancer cells.

PeerJ 2021 15;9:e11063. Epub 2021 Apr 15.

Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia.

Background: oncogenes harboring codon G12 and G13 substitutions are considered gatekeeper mutations which drive oncogenesis in many cancers. To date, there are still no target-specific vaccines or drugs available against this genotype, thus reinforcing the need towards the development of targeted therapies such as immunotoxins.

Methods: This study aims to develop a recombinant anti-m scFv-fused mutant actinoporin-like-toxin-1 (mHALT-1) immunotoxin that is capable of recognizing and eradicating codon-12 mutated k-ras antigen abnormal cells. Read More

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Tough Adhesion of Freezing- and Drying-Tolerant Transparent Nanocomposite Organohydrogels.

ACS Appl Mater Interfaces 2021 May 29;13(18):21822-21830. Epub 2021 Apr 29.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

Tough hydrogels with strong wet adhesion have drawn extensive attention for various applications. However, it is still challenging to achieve both excellent wet adhesion and freezing- and drying-tolerance in hydrogels. In this study, we present tough transparent nanocomposite organohydrogels based on the glycerol-water binary solvent system in the presence of Al(OH) nanoparticles as a cross-linker. Read More

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Two-Dimensional Covalent Organic Framework Solid Solutions.

J Am Chem Soc 2021 May 28;143(18):7081-7087. Epub 2021 Apr 28.

Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208 United States.

Covalent organic frameworks (COFs) generally leverage one or two monomers with specific sizes and shapes to access highly symmetric and periodic polymer networks. Almost all reported COFs employ the minimum sets of monomers needed for the polymerization (usually two, sometimes one) and crystallize in high-symmetry topologies. COFs synthesized from more than two monomers usually employ mixtures with different pendant functionalities to distribute these groups statistically throughout the structure, or monomers with different sizes in ratios targeting lower symmetry topologies. Read More

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Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells.

Nat Med 2021 Apr 22. Epub 2021 Apr 22.

Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

While CD19-directed chimeric antigen receptor (CAR) T cells can induce remission in patients with B cell acute lymphoblastic leukemia (ALL), a large subset relapse with CD19 disease. Like CD19, CD22 is broadly expressed by B-lineage cells and thus serves as an alternative immunotherapy target in ALL. Here we present the composite outcomes of two pilot clinical trials ( NCT02588456 and NCT02650414 ) of T cells bearing a 4-1BB-based, CD22-targeting CAR in patients with relapsed or refractory ALL. Read More

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A Novel Bispecific Antibody Targeting EGFR and VEGFR2 Is Effective against Triple Negative Breast Cancer via Multiple Mechanisms of Action.

Cancers (Basel) 2021 Mar 1;13(5). Epub 2021 Mar 1.

Division of Biotechnology Review and Research 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.

Both EGFR and VEGFR2 frequently overexpress in TNBC and cooperate with each other in autocrine and paracrine manner to enhance tumor growth and angiogenesis. Therapeutic mAbs targeting EGFR (cetuximab) and VEGFR2 (ramucirumab) are approved by FDA for numerous cancer indications, but none of them are approved to treat breast cancers. TNBC cells secrete VEGF-A, which mediates angiogenesis on endothelial cells in a paracrine fashion, as well as promotes cancer cell growth in autocrine manner. Read More

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Mapping and engineering of auxin-induced plasma membrane dissociation in BRX family proteins.

Plant Cell 2021 Mar 5. Epub 2021 Mar 5.

Department of Plant Molecular Biology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland.

Angiosperms have evolved the phloem for the long-distance transport of metabolites. The complex process of phloem development involves genes that only occur in vascular plant lineages. For example, in Arabidopsis thaliana, the BREVIS RADIX (BRX) gene is required for continuous root protophloem differentiation, together with PROTEIN KINASE ASSOCIATED WITH BRX (PAX). Read More

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A 3D Silverton-Type Polyoxomolybdate Based on {PrMoO}: Synthesis, Structure, Photoluminescence and Magnetic Properties.

Front Chem 2021 19;9:615595. Epub 2021 Feb 19.

Henan Key Laboratory of Polyoxometalate Chemistry, Institute of Molecular and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, China.

A three-dimensional (3D) Silverton-type polyoxomolybdate (POMo) with the formula of NH{Mn[PrMoO]}·18HO (1) was successfully isolated and well characterized by single crystal X-ray diffraction, X-ray powder diffraction pattern, infrared spectrum, thermogravimetric and elemental analyses. The inorganic building block {PrMoO} has formed 3D frameworks the {MnO} linker. The excitation of compound 1 in solid state at 375 nm displays red emission. Read More

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February 2021

Bispecific antibody therapy, its use and risks for infection: Bridging the knowledge gap.

Blood Rev 2021 Feb 27:100810. Epub 2021 Feb 27.

Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.

Relapsed haematological malignancies have a poor disease prognosis with current therapies. Bispecific antibodies (BsAbs) are becoming increasingly recognised for their efficacy in the treatment of these malignancies and are approved for the treatment of B-cell acute lymphoblastic leukaemia (B-ALL). BsAbs are manufactured to consist two variable chain fragments combined by a peptide linker amongst other structures to increase the half-life of the molecules. Read More

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February 2021

Preparation and characterization of 96-well microplates coated with molecularly imprinted polymer for determination and biosimilarity assessment of recombinant human erythropoietin.

J Chromatogr A 2021 Mar 18;1641:462012. Epub 2021 Feb 18.

Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Egypt.

Synthesis and applications of molecularly imprinted polymers (MIP) are rapidly growing. In this study, a biomimetic MIP was prepared through silanes polymerization on the surface of 96-well microplates using recombinant human erythropoietin-alfa (rhEPO) as a template molecule. The rhEPO was immobilized onto the plate surface using bi-functional cross-linker and a thin imprinted layer following sol-gel procedure was constructed. Read More

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Tacrine-sugar mimetic conjugates as enhanced cholinesterase inhibitors.

Org Biomol Chem 2021 03;19(10):2322-2337

Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, NO-4036 Stavanger, Norway.

We have used the Cu(i)-catalyzed azide-alkyne Huisgen cycloaddition reaction to obtain two families of bivalent heterodimers where tacrine is connected to an azasugar or iminosugar, respectively, via linkers of variable length. The heterodimers were investigated as cholinesterase inhibitors and it was found that their activity increased with the length of the linker. Two of the heterodimers were significantly stronger acetylcholinesterase inhibitors than the monomeric tacrine. Read More

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Ring-Opening Metathesis Polymerization of Norbornene-Based Monomers Obtained via the Passerini Three Component Reaction.

Macromol Rapid Commun 2021 May 1;42(9):e2100027. Epub 2021 Mar 1.

Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber-Weg 6, Karlsruhe, 76131, Germany.

Ring-opening metathesis polymerization is a robust method to synthesize a variety of polymers by using ring-strained molecules as monomers, e.g., norbornenes. Read More

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Cyclic gallium-68 labeled peptides for specific detection of human angiotensin-converting enzyme 2.

J Nucl Med 2021 Feb 26. Epub 2021 Feb 26.

UCSF, United States.

In this study, we developed ACE2-specific, peptide-derived Ga-labeled radiotracers, motivated by the hypotheses that (1) ACE2 is an important determinant of SARS-CoV-2 susceptibility, and (2) that modulation of ACE2 in COVID-19 drives severe organ injury. A series of NOTA-conjugated peptides derived from the known ACE2 inhibitor DX600 were synthesized, with variable linker identity. Since DX600 bears two cystine residues, both linear and cyclic peptides were studied. Read More

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February 2021

A rainbow of acridinium chemiluminescence.

Luminescence 2021 Jun 9;36(4):1097-1106. Epub 2021 Mar 9.

Applied Research and Technology, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, Illinois, USA.

Multicolor chemiluminescent acridinium derivatives were synthesized by attaching various common fluorophores to the N -acridinium position through a piperazine linker. Triggering of each acridinium derivative using alkaline hydrogen peroxide resulted in a chemiluminescence spectrum dominated by a strong emission (>95%) from the attached fluorophore. The highly quenched emission from the triggered acridinium, acting as a donor, points to a highly efficient intramolecular energy transfer in acridinium-based chemiluminophore-fluorophore tandems. Read More

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Responses of Defect-Rich Zr-Based Metal-Organic Frameworks toward NH Adsorption.

J Am Chem Soc 2021 Mar 17;143(8):3205-3218. Epub 2021 Feb 17.

Wolfson Catalysis Centre, Department of Chemistry, University of Oxford, Oxford OX1 3QR, U.K.

Understanding structural responses of metal-organic frameworks (MOFs) to external stimuli such as the inclusion of guest molecules and temperature/pressure has gained increasing attention in many applications, for example, manipulation and manifesto smart materials for gas storage, energy storage, controlled drug delivery, tunable mechanical properties, and molecular sensing, to name but a few. Herein, neutron and synchrotron diffractions along with Rietveld refinement and density functional theory calculations have been used to elucidate the responsive adsorption behaviors of defect-rich Zr-based MOFs upon the progressive incorporation of ammonia (NH) and variable temperature. UiO-67 and UiO-bpydc containing biphenyl dicarboxylate and bipyridine dicarboxylate linkers, respectively, were selected, and the results establish the paramount influence of the functional linkers on their NH affinity, which leads to stimulus-tailoring properties such as gate-controlled porosity by dynamic linker flipping, disorder, and structural rigidity. Read More

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Fluorescence depolarization dynamics of ionic strength sensors using time-resolved anisotropy.

Biophys J 2021 Apr 12;120(8):1417-1430. Epub 2021 Feb 12.

Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, Minnesota. Electronic address:

Eukaryotic cells exploit dynamic and compartmentalized ionic strength to impact a myriad of biological functions such as enzyme activities, protein-protein interactions, and catalytic functions. Herein, we investigated the fluorescence depolarization dynamics of recently developed ionic strength biosensors (mCerulean3-linker-mCitrine) in Hofmeister salt (KCl, NaCl, NaI, and NaSO) solutions. The mCerulean3-mCitrine acts as a Förster resonance energy transfer (FRET) pair, tethered together by two oppositely charged α-helices in the linker region. Read More

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Generation and functional characterization of a single-chain variable fragment (scFv) of the anti-FGF2 3F12E7 monoclonal antibody.

Sci Rep 2021 Jan 14;11(1):1432. Epub 2021 Jan 14.

Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100 - Vila Clementino, São Paulo, SP, CEP 04044-020, Brazil.

Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. Read More

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January 2021

Encapsulation and Controlled Release of a Camptothecin Prodrug from Nanocarriers and Microgels: Tuning Release Rate with Nanocarrier Excipient Composition.

Mol Pharm 2021 03 13;18(3):1093-1101. Epub 2021 Jan 13.

Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544, United States.

Nanocarriers (NCs) are an attractive class of vehicles for drug delivery with the potential to improve drug efficacy and safety, particularly for intravenous parenteral delivery. Many therapeutics remain challenging to formulate in NCs due to their intrinsic solubilities that frustrate NC loading or result in too rapid release . Therapeutic conjugate approaches that alter the solubility of a conjugate "prodrug" have been used to enable NC formation and controlled release from NCs using labile linker chemistry. Read More

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Dimeric Cycloparaphenylenes with a Rigid Aromatic Linker.

Angew Chem Int Ed Engl 2021 Mar 26;60(14):7649-7653. Epub 2021 Feb 26.

Institute of Molecular Plus, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Tianjin University, 92 Weijin Road, Tianjin, 300072, China.

Dimeric cycloparaphenylene (CPP) architectures with well-defined flipping motion are constructed taking advantage of an efficient cyclocondensation reaction. Variable-temperature nuclear magnetic resonance (VT-NMR) analyses and theoretical calculations indicate rapid interconversion of cis and trans conformers at room temperature, while energetically favorable trans conformer exists at low temperature with the metastable cis conformer hidden. The trihexylsilylethynyl-substituted dimer exhibits bright emission in solution at 616 nm with quantum yield up to 80 %, representing the brightest CPP-based emitter beyond 600 nm. Read More

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Construction and application of a human scFv phage display library based on Cre‑LoxP recombination for anti‑PCSK9 antibody selection.

Int J Mol Med 2021 Feb 16;47(2):708-718. Epub 2020 Dec 16.

Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, Jilin 132013, P.R. China.

A large human natural single‑chain fragment variable (scFv) phage library was constructed based on Cre‑LoxP recombination, and used to successfully identify antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). The library was derived from 400 blood samples, 30 bone marrow samples, and 10 cord blood samples from healthy donors. Lymphocytes were isolated from each sample and cDNA was synthesized using reverse transcription‑quantitative PCR. Read More

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February 2021

[Preparation of anti-GPC3 single chain antibody for targeted detection of hepatocellular carcinoma].

Sheng Wu Gong Cheng Xue Bao 2020 Dec;36(12):2860-2867

State key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.

Glypican-3 (GPC3) is a key member of Glypican family and plays an important role in the development, angiogenesis and metastasis of hepatocellular carcinoma (HCC). Most HCC overexpresses GPC3, but GPC3 is hardly detected in normal adult liver and benign liver lesions, so it is regarded as a highly specific diagnostic marker and an ideal therapeutic target for HCC. In this study, we cloned the heavy and light chain variable region gene from the monoclonal antibody targeted to GPC3 screened in the previous stage, and linked it with a segment of flexible peptide (Linker) to obtain the single chain antibody against GPC3. Read More

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December 2020

Synthesis of σ Receptor Ligands with a Spirocyclic System Connected with a Tetrahydroisoquinoline Moiety via Different Linkers.

ChemMedChem 2021 Apr 2;16(7):1184-1197. Epub 2021 Feb 2.

Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstr. 48, 48149, Münster, Germany.

With the aim to develop new σ receptor ligands, spirocyclic piperidines or cyclohexanamines with 2-benzopyran and 2-benzofuran scaffolds were connected to the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline moiety by variable linkers. In addition to flexible alkyl chains, linkers containing an amide as functional group were synthesized. The 2-benzopyran and 2-benzofuran scaffold of the spirocyclic compounds were synthesized from 2-bromobenzaldehyde. Read More

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QSAR and molecular docking for the search of AOX inhibitors: a rational drug discovery approach.

J Comput Aided Mol Des 2021 Feb 8;35(2):245-260. Epub 2020 Dec 8.

Department of Biochemistry and Biomedicine, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.

The alternative oxidase (AOX) is a monotopic diiron carboxylate protein that catalyses the oxidation of ubiquinol and the reduction of oxygen to water. Although a number of AOX inhibitors have been discovered, little is still known about the ligand-protein interaction and essential chemical characteristics of compounds required for a potent inhibition. Furthermore, owing to the rapidly growing resistance to existing inhibitors, new compounds with improved potency and pharmacokinetic properties are urgently required. Read More

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February 2021

Chicken antibodies against venom proteins of in Taiwan.

J Venom Anim Toxins Incl Trop Dis 2020 Nov 20;26:e20200056. Epub 2020 Nov 20.

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

Background: The venom of bamboo vipers ( - TS), commonly found in Taiwan, contains deadly hemotoxins that cause severe envenomation. Equine-derived antivenom is a specific treatment against snakebites, but its production costs are high and there are some inevitable side effects. The aim of the present work is to help in the development of an affordable and more endurable therapeutic strategy for snakebites. Read More

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November 2020

Structural integrity, meltability, and variability of thermal properties in the mixed-linker zeolitic imidazolate framework ZIF-62.

J Chem Phys 2020 Nov;153(20):204501

Otto Schott Institute of Materials Research, University of Jena, Jena, Germany.

Metal-organic framework (MOF) glasses have emerged as a new class of melt-quenched glasses; however, so far, all MOF glass production has remained at lab-scale; future applications will require large-scale, commercial production of parent crystalline MOFs. Yet, control of synthetic parameters, such as uniform temperature and mixing, can be challenging, particularly, when scaling-up production of a mixed-linker MOF or a zeolitic imidazolate framework (ZIF). Here, we examine the effect of heterogeneous linker distribution on the thermal properties and melting behavior of ZIF-62. Read More

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November 2020

High resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies.

bioRxiv 2020 Nov 16. Epub 2020 Nov 16.

Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, Spike (S). Here we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using COVID-19 convalescent plasma. Read More

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November 2020

Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development.

Front Chem 2020 25;8:696. Epub 2020 Aug 25.

Facultad de Ciencias Bioquímicas y Farmacéuticas, Instituto de Química de Rosario (IQUIR), Universidad Nacional de Rosario, Rosario, Argentina.

L-Proline is an important amino acid for the pathogenic protists belonging to and genera. In , the etiological agent of Chagas disease, this amino acid is involved in fundamental biological processes such as ATP production, differentiation of the insect and intracellular stages, the host cell infection and the resistance to a variety of stresses. In this study, we explore the L-Proline uptake as a chemotherapeutic target for . Read More

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Co(II) Macrocyclic Complexes Appended with Fluorophores as paraCEST and cellCEST Agents.

Inorg Chem 2020 Nov 2;59(22):16531-16544. Epub 2020 Nov 2.

Department of Chemistry, University at Buffalo, the State University of New York, Amherst, New York 14260, United States.

Four high-spin macrocyclic Co(II) complexes with hydroxypropyl or amide pendants and appended coumarin or carbostyril fluorophores were prepared as CEST (chemical exchange saturation transfer) MRI probes. The complexes were studied in solution as paramagnetic CEST (paraCEST) agents and after loading into yeast cells as cell-based CEST (cellCEST) agents. The fluorophores attached to the complexes through an amide linkage imparted an unusual pH dependence to the paraCEST properties of all four complexes through of ionization of a group that was attributed to the amide NH linker. Read More

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November 2020

Identification of a linear epitope within domain I of Duck Tembusu virus envelope protein using a novel neutralizing monoclonal antibody.

Dev Comp Immunol 2021 Feb 28;115:103906. Epub 2020 Oct 28.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, 430070, China. Electronic address:

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that caused severe egg drop syndrome in laying ducks in China since 2010, leading to massive economic losses to the duck industry. Although the DTMUV E protein is considered to be critical in inducing the protective immune response, the functional epitopes within this protein remain largely unknown. In the present study, we isolated a DTMUV neutralizing monoclonal antibody (mAb) 3B8 from DTMUV E-immunized mice. Read More

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February 2021

Soft Mode Metal-Linker Dynamics in Carboxylate MOFs Evidenced by Variable-Temperature Infrared Spectroscopy.

J Am Chem Soc 2020 11 29;142(45):19291-19299. Epub 2020 Oct 29.

Department of Chemistry and Biochemistry, Materials Science Institute, University of Oregon, Eugene, Oregon 97403-1253, United States.

Through comprehensive analysis of carboxylate-based metal-organic frameworks (MOFs), we present general evidence that challenges the common perception of MOF metal-linker bonds being static. Structural dynamics in MOFs, however, typically refers to the "breathing" behavior of cavities, where pores open and close in response to guest molecules, and to the transient binding of guest molecules, but dynamic bonding would explain important MOF phenomena in catalysis, postsynthetic exchange, negative thermal expansion, and crystal growth. Here, we demonstrate, through use of variable-temperature diffuse reflectance infrared Fourier transform spectroscopy (VT-DRIFTS) aided by ab initio plane wave density functional theory, that similar evidence for melting behavior in zeolitic imidazolate frameworks (ZIFs), i. Read More

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November 2020

Structural Model of the Proline-Rich Domain of Huntingtin Exon-1 Fibrils.

Biophys J 2020 11 20;119(10):2019-2028. Epub 2020 Oct 20.

Department of Physiology & Neuroscience, Zilkha Neurogenetic Institute, Keck School of Medicine of USC, Los Angeles, California. Electronic address:

Huntington's disease is a heritable neurodegenerative disease that is caused by a CAG expansion in the first exon of the huntingtin gene. This expansion results in an elongated polyglutamine domain that increases the propensity of huntingtin exon-1 to form cross-β fibrils. Although the polyglutamine domain is important for fibril formation, the dynamic, C-terminal proline-rich domain (PRD) of huntingtin exon-1 makes up a large fraction of the fibril surface. Read More

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November 2020