9,770 results match your criteria linker sequence

Development and characterization of two novel Ga labelled Neuropeptide Y short analogues with potential application in breast cancer imaging.

Chem Biol Drug Des 2021 May 12. Epub 2021 May 12.

Área de Radioquímica, Departamento Estrella Campos, Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for Molecular Imaging. This work presents the development and characterisation of two novel Neuropeptide Y analogues labelled with a positron emitter Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatised with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). Read More

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Self-assembly of multiferroic core-shell composites using DNA functionalized nanoparticles.

J Magn Magn Mater 2018 Aug 4;460:424-431. Epub 2018 Apr 4.

Department of Physics, Oakland University, Rochester, MI 48309-4401, United States.

Ferrite-ferroelectric core-shell nanoparticles were prepared by deoxyribonucleic acid (DNA) assisted self-assembly and the strained mediated magneto-electric (ME) interactions between the ferroic phases were studied. The nanoparticle type and size were varied and the DNA linker sequence was also varied. Two kinds of particles, one with 600 nm barium titanate (BTO) core and 200 nm nickel ferrite (NFO) shell and another with 200 nm BTO core and 50 nm nickel cobalt ferrite (NCFO) shell were prepared. Read More

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Structure elements can be predicted using the contact volume among protein residues.

Biophys Physicobiol 2021 18;18:50-59. Epub 2021 Feb 18.

Division of Materials Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan.

Previously, the structure elements of dihydrofolate reductase (DHFR) were determined using comprehen-sive Ala-insertion mutation analysis, which is assumed to be a kind of protein "building blocks." It is hypo-thesized that our comprehension of the structure elements could lead to understanding how an amino acid sequence dictates its tertiary structure. However, the comprehensive Ala-insertion mutation analysis is a time- and cost-consuming process and only a set of the DHFR structure elements have been reported so far. Read More

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February 2021

Syntheses of Morpholine-Based Nucleotide Analogs for Hepatic siRNA Targeting and Stabilization.

J Med Chem 2021 May 5. Epub 2021 May 5.

Sanofi R&D, Industrial Park Hoechst, G838, Frankfurt am Main 65926, Germany.

A morpholine-based nucleotide analog was developed as a building block for hepatic siRNA targeting and stabilization. Attachment of an asialoglycoprotein-binding GalNAc ligand at the morpholine nitrogen was realized with different linkers. The obtained morpholino GalNAc scaffolds were coupled to the sense strand of a transthyretin-targeting siRNA and tested for their knockdown potency and . Read More

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Essential Roles of the Linker Sequence Between Tetratricopeptide Repeat Motifs of Ethylene Overproduction 1 in Ethylene Biosynthesis.

Front Plant Sci 2021 15;12:657300. Epub 2021 Apr 15.

College of Horticulture, Northwest A&F University, Yangling, China.

Ethylene Overproduction 1 (ETO1) is a negative regulator of ethylene biosynthesis. However, the regulation mechanism of ETO1 remains largely unclear. Here, a novel allele () was isolated with typical triple phenotypes due to an amino acid substitution of G480C in the uncharacterized linker sequence between the TPR1 and TPR2 motifs. Read More

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The 'Shape-Shifter' Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences.

Biomolecules 2021 Apr 26;11(5). Epub 2021 Apr 26.

Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.

Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, β-strand and loop conformations. This region has been called a 'shape-shifter' peptide. Characterisation of this peptide using NMR experiments and MD simulations has shown that it is essentially disordered in solution. Read More

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Phosphopeptide interactions of the Nbs1 N-terminal FHA-BRCT1/2 domains.

Sci Rep 2021 Apr 27;11(1):9046. Epub 2021 Apr 27.

Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, 27709, USA.

Human Nbs1, a component of the MRN complex involved in DNA double strand break repair, contains a concatenated N-terminal FHA-BRCT1/2 sequence that supports interaction with multiple phosphopeptide binding partners. MDC1 binding localizes Nbs1 to the damage site, while binding of CDK-phosphorylated CtIP activates additional ATM-dependent CtIP phosphorylation, modulating substrate-dependent resection. We have investigated the phosphopeptide binding characteristics of Nbs1 BRCT1/2 based on a molecular modeling approach that revealed structural homology with the tandem TopBP1 BRCT7/8 domains. Read More

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Enhancement of direct electron transfer in graphene bioelectrodes containing novel cytochrome c variants with optimized heme orientation.

Bioelectrochemistry 2021 Apr 8;140:107818. Epub 2021 Apr 8.

Solar Fuels Laboratory, Center of New Technologies, University of Warsaw, Banacha 2C, 02-097 Warsaw, Poland. Electronic address:

The highly efficient bioelectrodes based on single layer graphene (SLG) functionalized with pyrene self-assembled monolayer and novel cytochromec(cytc)peptide linker variants were rationally designed to optimize the direct electron transfer (DET) between SLG and the heme group of cyt. Through a combination of photoelectrochemical and quantum mechanical (QM/MM) approaches we show that the specific amino acid sequence of a short peptide genetically inserted between the cytcholoprotein and thesurface anchoring C-terminal His-tag plays a crucial role in ensuring the optimal orientation and distance of the heme group with respect to the SLG surface. Consequently, efficient DET occurring between graphene and cyt c leads to a 20-fold enhancement of the cathodic photocurrent output compared to the previously reported devices of a similar type. Read More

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Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.

Nat Commun 2021 04 23;12(1):2426. Epub 2021 Apr 23.

Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.

To adapt to fluctuating protein folding loads in the endoplasmic reticulum (ER), the Hsp70 chaperone BiP is reversibly modified with adenosine monophosphate (AMP) by the ER-resident Fic-enzyme FICD/HYPE. The structural basis for BiP binding and AMPylation by FICD has remained elusive due to the transient nature of the enzyme-substrate-complex. Here, we use thiol-reactive derivatives of the cosubstrate adenosine triphosphate (ATP) to covalently stabilize the transient FICD:BiP complex and determine its crystal structure. Read More

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Lanthanide-based resonance energy transfer biosensors for live-cell applications.

Methods Enzymol 2021 23;651:291-311. Epub 2021 Feb 23.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL, United States. Electronic address:

Lanthanide-based, Förster resonance energy transfer (LRET) biosensors enable sensitive, time-gated luminescence (TGL) imaging or multiwell plate analysis of protein-protein interactions (PPIs) in living mammalian cells. LRET biosensors are polypeptides that consist of an alpha-helical linker sequence sandwiched between a lanthanide complex-binding domain and a fluorescent protein (FP) with two interacting domains residing at each terminus. Interaction between the terminal affinity domains brings the lanthanide complex and FP in close proximity such that lanthanide-to-FP, LRET-sensitized emission is increased. Read More

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February 2021

Femtomolar Detection of Thrombin in Serum and Cerebrospinal Fluid via Direct Electrocatalysis of Oxygen Reduction by the Covalent G4-Hemin-Aptamer Complex.

ACS Appl Mater Interfaces 2021 Apr 20. Epub 2021 Apr 20.

Interdisciplinary Nanoscience Center (iNANO), Science and Technology, Aarhus University, Gustav Wieds Vej 1590-14, Aarhus C DK-8000, Denmark.

Thrombin, a serine protease playing a central role in the coagulation cascade reactions and a potent neurotoxin produced by injured brain endothelial cells, is a recognized cardiac biomarker and a critical biomarker for Alzheimer's disease development. Both in vivo and in vitro, its low physiological concentrations and nonspecific binding of other components of physiological fluids complicate electroanalysis of thrombin. Here, femtomolar levels of thrombin in serum and an artificial cerebrospinal fluid (CSF) were detected by the indicator-free electrochemical methodology exploiting the O reduction reaction directly, with no electron transfer mediators, electrocatalyzed by the covalent G4-hemin DNAzyme complex naturally self-assembling upon thrombin binding to the hemin-modified 29-mer DNA aptamer sequence tethered to gold via an alkanethiol linker. Read More

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Combining Benzazolo-Oxazolidine Twins toward Multi-state Nonlinear Optical Switches.

J Phys Chem B 2021 Apr 14;125(15):3918-3931. Epub 2021 Apr 14.

Theoretical Chemistry Laboratory, Unit of Theoretical and Structural Physical Chemistry, Namur Institute of Structured Matter, University of Namur, B-5000 Namur, Belgium.

Molecular switches are chemical compounds exhibiting the possibility of reversible transformations between their different forms accompanied by a modification in their properties. Among these, switching of multi-addressable Benzazolo-OXazolidines (BOXs) from a closed form to an open form results in drastic modifications in their linear and nonlinear optical properties. Here, we target molecules containing two identical BOX units (DiBOX) connected by different π-conjugated linkers, and we combine synthesis, UV/visible absorption, and hyper-Rayleigh scattering (HRS) measurements, together with density functional theory (DFT) calculations. Read More

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Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase.

Nat Commun 2021 04 12;12(1):2162. Epub 2021 Apr 12.

Structural Biology, Biozentrum, University of Basel, Basel, Switzerland.

Diguanylate cyclases synthesising the bacterial second messenger c-di-GMP are found to be regulated by a variety of sensory input domains that control the activity of their catalytical GGDEF domain, but how activation proceeds mechanistically is, apart from a few examples, still largely unknown. As part of two-component systems, they are activated by cognate histidine kinases that phosphorylate their Rec input domains. DgcR from Leptospira biflexa is a constitutively dimeric prototype of this class of diguanylate cyclases. Read More

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Structural insights into the ligand recognition and catalysis of the key aminobutanoyltransferase CntL in staphylopine biosynthesis.

FASEB J 2021 May;35(5):e21575

Research Center for Drug Discovery and Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

Staphylopine (StP) and other nicotianamine-like metallophores are crucial for many pathogens to acquire the transition metals from hosts during invasion. CntL from Staphylococcus aureus (SaCntL) catalyzes the condensation of the 2-aminobutyrate (Ab) moiety of S-adenosylmethionine (SAM) with D-histidine in the biosynthesis of StP. Here, we report the crystal structures of SaCntL in complex with either SAM or two products. Read More

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Genotyping of Deltamethrin Resistance in Rhipicephalus (Boophilus) microplus Population in Kerala, South India.

Acta Parasitol 2021 Apr 3. Epub 2021 Apr 3.

School of Applied Animal Production and Biotechnology, College of Veterinary and Animal Sciences, Kerala Veterinary and Animal Sciences University, Mannuthy, Thrissur, Kerala, 680651, India.

Purpose: Genotyping of Rhipicephalus (Boophilus) microplus for polymorphisms in deltamethrin-resistant loci of sodium channel gene by allele-specific PCR (AS-PCR).

Methods: Adult R. (B. Read More

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PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αβ Receptors.

Molecules 2021 Mar 22;26(6). Epub 2021 Mar 22.

Radiochemical Studies Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research "Demokritos", Ag. Paraskevi Attikis, 15310 Athens, Greece.

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin αβ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin αβ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. Read More

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Recent Advances and Trends in Chemical CPP-Drug Conjugation Techniques.

Molecules 2021 Mar 13;26(6). Epub 2021 Mar 13.

Department of Chemistry, Institute for Biochemistry, University of Cologne, Zuelpicher str. 47a, D-50674 Cologne, Germany.

This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)-drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. Read More

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Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Biomolecules 2021 03 15;11(3). Epub 2021 Mar 15.

Department of Health Science and Social Welfare, Kibi International University, Takahashi 716-8508, Japan.

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. Read More

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Molecular Characterization of Three B-1,4-Endoglucanase Genes in and Functional Analysis of -2 Gene.

Plants (Basel) 2021 Mar 17;10(3). Epub 2021 Mar 17.

Istituto per la Protezione Sostenibile delle Piante (IPSP), Consiglio Nazionale delle Ricerche (CNR), S.S. Bari, Via G. Amendola 122/D, 70126 Bari, Italy.

is an important root-lesion nematode that causes damage to tea plantations in Iran and all over the world. The present study reports on the characterization and evolution of three ß-1,4-endoglucanase genes: -2, -3 and -4. The gene structure of -2 was fully determined with the predicted signal peptide and devoid of the linker domain and carbohydrate-binding domain, while -3 and -4 were only partially sequenced. Read More

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Exploring Obscurin and SPEG Kinase Biology.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Centre for Molecular and Translational Medicine, The Wallenberg Laboratory and Wallenberg, Department of Molecular and Clinical Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.

Three members of the obscurin protein family that contain tandem kinase domains with important signaling functions for cardiac and striated muscles are the giant protein obscurin, its obscurin-associated kinase splice isoform, and the striated muscle enriched protein kinase (SPEG). While there is increasing evidence for the specific roles that each individual kinase domain plays in cross-striated muscles, their biology and regulation remains enigmatic. Our present study focuses on kinase domain 1 and the adjacent low sequence complexity inter-kinase domain linker in obscurin and SPEG. Read More

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Incorporation of a nucleoside analog maps genome repair sites in postmitotic human neurons.

Science 2021 04;372(6537):91-94

Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1002, USA.

Neurons are the longest-lived cells in our bodies and lack DNA replication, which makes them reliant on a limited repertoire of DNA repair mechanisms to maintain genome fidelity. These repair mechanisms decline with age, but we have limited knowledge of how genome instability emerges and what strategies neurons and other long-lived cells may have evolved to protect their genomes over the human life span. A targeted sequencing approach in human embryonic stem cell-induced neurons shows that, in neurons, DNA repair is enriched at well-defined hotspots that protect essential genes. Read More

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The glucoamylase from Aspergillus wentii: Purification and characterization.

J Basic Microbiol 2021 May 30;61(5):443-458. Epub 2021 Mar 30.

Department of Biochemistry, Universidade Estadual de Maringá, Maringá, Paraná, Brazil.

This study describes for the first time the purification and characterization of a glucoamylase from Aspergillus wentii (strain PG18), a species of the Aspergillus genus Cremei section. Maximum enzyme production (∼3.5 U/ml) was obtained in submerged culture (72 h) with starch as the carbon source, at 25°C, and with orbital agitation (100 rpm). Read More

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Resolving the activation mechanism of the D99N antiterminator LicT protein.

J Struct Biol 2021 Mar 27;213(2):107730. Epub 2021 Mar 27.

CBS, Univ Montpellier, CNRS, INSERM, Montpellier, France. Electronic address:

LicT is an antiterminator protein of the BglG family whose members are key players in the control of carbohydrate catabolism in bacteria. These antiterminators are generally composed of three modules, an N-terminal RNA-binding domain (CAT) followed by two homologous regulation modules (PRD1 and PRD2) that control the RNA binding activity of the effector domain via phosphorylation on conserved histidines. Although several structures of isolated domains of BglG-like proteins have been described, no structure containing CAT and at least one PRD simultaneously has yet been reported in an active state, precluding detailed understanding of signal transduction between modules. Read More

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Scaffolding proteins guide the evolution of algal light harvesting antennas.

Nat Commun 2021 03 25;12(1):1890. Epub 2021 Mar 25.

School of Physics, University of New South Wales, Sydney, NSW, 2052, Australia.

Photosynthetic organisms have developed diverse antennas composed of chromophorylated proteins to increase photon capture. Cryptophyte algae acquired their photosynthetic organelles (plastids) from a red alga by secondary endosymbiosis. Cryptophytes lost the primary red algal antenna, the red algal phycobilisome, replacing it with a unique antenna composed of αβ protomers, where the β subunit originates from the red algal phycobilisome. Read More

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Discovery of novel tetrahydrobenzo[b]thiophene-3-carbonitriles as histone deacetylase inhibitors.

Bioorg Chem 2021 May 5;110:104801. Epub 2021 Mar 5.

Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India. Electronic address:

The discovery and development of isoform-selective histone deacetylase (HDAC) inhibitor is a challenging task because of the sequence homology among HDAC enzymes. In the present work, novel tetrahydro benzo[b]thiophene-3-carbonitrile based benzamides were designed, synthesized, and evaluated as HDAC inhibitors. Pharmacophore modeling was our main design strategy, and two novel series of tetrahydro benzo[b]thiophene-3-carbonitrile derivatives with piperidine linker (series 1) and piperazine linker (series 2) were identified as HDAC inhibitors. Read More

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Curvature sensing amphipathic helix in the C-terminus of RTNLB13 is conserved in all endoplasmic reticulum shaping reticulons in Arabidopsis thaliana.

Sci Rep 2021 Mar 18;11(1):6326. Epub 2021 Mar 18.

Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.

The reticulon family of integral membrane proteins are conserved across all eukaryotes and typically localize to the endoplasmic reticulum (ER), where they are involved in generating highly-curved tubules. We recently demonstrated that Reticulon-like protein B13 (RTNLB13) from Arabidopsis thaliana contains a curvature-responsive amphipathic helix (APH) important for the proteins' ability to induce curvature in the ER membrane, but incapable of generating curvature by itself. We suggested it acts as a feedback element, only folding/binding once a sufficient degree of curvature has been achieved, and stabilizes curvature without disrupting the bilayer. Read More

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Simplified plasmid cloning with a universal MCS design and bacterial in vivo assembly.

BMC Biotechnol 2021 Mar 15;21(1):24. Epub 2021 Mar 15.

School of Biological Science and Biotechnology, Minnan Normal University, Zhangzhou, 363000, P.R. China.

Background: The ability to clone DNA sequences quickly and precisely into plasmids is essential for molecular biology studies. The recent development of seamless cloning technologies has made significant improvements in plasmid construction, but simple and reliable tools are always desirable for time- and labor-saving purposes.

Results: We developed and standardized a plasmid cloning protocol based on a universal MCS (Multiple Cloning Site) design and bacterial in vivo assembly. Read More

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A Homogeneous Multicomponent Nucleic Acid Enzyme Assay for Universal Nucleic Acid Detection by Single-Particle Inductively Coupled Plasma Mass Spectrometry.

Anal Chem 2021 03 9;93(11):4952-4959. Epub 2021 Mar 9.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, China.

Single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) has great potential for sensitive analysis of nucleic acids; however, it usually requires separation of target-induced nanoparticle reporters, and the sequence of probes on nanoparticle reporters has to be tuned for each target accordingly. Here, we developed a homogeneous multicomponent nucleic acid enzyme (MNAzyme) assay for universal nucleic acid detection. The two components of MNAzyme contain target recognition sites, substrate binding sites, and a catalytic core. Read More

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Graphene Oxide-Gold Star Construct on Triangular Electrodes for Alzheimer's Disease Identification.

J Anal Methods Chem 2021 22;2021:6661799. Epub 2021 Feb 22.

Department of First Neurology, Baoding No.1 Central Hospital, Baoding, Hebei 071000, China.

Nanotechnology is playing a major role in the field of medical diagnosis, in particular with the biosensor and bioimaging. It improves the performance of the desired system dramatically by displaying higher selectivity and sensitivity. Carbon nanomaterial, gold nanostructure, magnetite nanoparticle, and silica substrate are the most popular nanomaterials greatly contributed to make the affordable and effective biosensor at low-cost. Read More

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February 2021

The design of multiepitope vaccines from plasmids of diarrheagenic Escherichia coli against diarrhoea infection: Immunoinformatics approach.

Infect Genet Evol 2021 Mar 5;91:104803. Epub 2021 Mar 5.

Discipline of Chemical Engineering, University of KwaZulu-Natal, Howard Campus, Durban 4041, South Africa.

Diarrhoea infection is a major global health public problem and is caused by many organisms including diarrheagenic Escherichia coli pathotypes. The common problem with diarrhoea is the drug resistance of pathogenic bacteria, the most promising alternative means of preventing drug resistance is vaccination. However, there has not been any significant success in the prevention of diarrhoea caused by E. Read More

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