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#32745829   2020/07/29 To Up

Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes.

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Linda Cerofolini, Marco Fragai, Claudio Luchinat, Enrico Ravera

1705 related Products with: Orientation of immobilized antigens on common surfaces by a simple computational model: Exposition of SARS-CoV-2 Spike protein RBD epitopes.

100 0.1 mg1mg100 20 ug Product tipe: Antib1mg300 1mg200 100 100 100

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#32745692   2020/07/31 To Up

Supramolecular Self-Assembling Peptides to Deliver Bone Morphogenetic Proteins for Skeletal Regeneration.

Recombinant human bone morphogenetic proteins (BMPs) have shown clinical success in promoting bone healing, but they are also associated with unwanted side effects. The development of improved BMP carriers that can retain BMP at the defect site and maximize its efficacy would decrease the therapeutic BMP dose and thus improve its safety profile. In this review, we discuss the advantages of using self-assembling peptides, a class of synthetic supramolecular biomaterials, to deliver recombinant BMPs. Peptide amphiphiles (PAs) are a broad class of self-assembling peptides, and the use of PAs for BMP delivery and bone regeneration has been explored extensively over the past decade. Like many self-assembling peptide systems, PAs can be designed to form nanofibrous supramolecular biomaterials in which molecules are held together by non-covalent bonds. Chemical and biological functionality can be added to PA nanofibers, through conjugation of chemical moieties or biological epitopes to PA molecules. For example, PA nanofibers have been designed to bind heparan sulfate, a natural polysaccharide that is known to bind BMPs and potentiate their signal. Alternatively, PA nanofibers have been designed to synthetically mimic the structure and function of heparan sulfate, or to directly bind BMP specifically. In small animal models, these bio-inspired PA materials have shown the capacity to promote bone regeneration using BMP at doses 10 - 100 times lower than established therapeutic doses. These promising results have motivated further evaluation of PAs in large animal models, where their safety and efficacy must be established before clinical translation. We conclude with a discussion on the possiblity of combining PAs with other materials used in orthopedic surgery to maximize their utility for clinical translation.
Charlotte H Chen, Erin L Hsu, Samuel I Stupp

1560 related Products with: Supramolecular Self-Assembling Peptides to Deliver Bone Morphogenetic Proteins for Skeletal Regeneration.

10ìg5 ug100ug100 ug20100 μg5 ug100ug50ug100ug100ug100ug

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#32745149   2020/08/03 To Up

Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step.

Human cytomegalovirus (HCMV) is one of the main causative agents of congenital viral infection in neonates. HCMV infection also causes serious morbidity and mortality among organ transplant patients. Glycoprotein B (gB) is a major target for HCMV neutralizing antibodies, yet the underlying neutralization mechanisms remain largely unknown. Here we report that 3-25, a gB-specific monoclonal antibody previously isolated from a healthy HCMV-positive donor, efficiently neutralized 14 HCMV strains in both ARPE-19 cells and MRC-5 cells. The core epitope of 3-25 was mapped to a highly conserved linear epitope on antigenic domain 2 (AD-2) of gB. A 1.8 Å crystal structure of 3-25 Fab in complex with the peptide epitope revealed the molecular determinants of 3-25 binding to gB at atomic resolution. Negative-staining electron microscopy (EM) 3D reconstruction of 3-25 Fab in complex with de-glycosylated postfusion gB showed that 3-25 Fab fully occupied the gB trimer at the N-terminus with flexible binding angles. Functionally, 3-25 efficiently inhibited HCMV infection at a post-attachment step by interfering with viral membrane fusion, and restricted post-infection viral spreading in ARPE-19 cells. Interestingly, bivalency was required for HCMV neutralization by AD-2 specific antibody 3-25 but not the AD-4 specific antibody LJP538. In contrast, bivalency was not required for HCMV binding by both antibodies. Taken together, our results reveal the structural basis of gB recognition by 3-25 and demonstrate that inhibition of viral membrane fusion and a requirement of bivalency may be common for gB AD-2 specific neutralizing antibody.
Xiaohua Ye, Hang Su, Daniel Wrapp, Daniel C Freed, Fengsheng Li, Zihao Yuan, Aimin Tang, Leike Li, Zhiqiang Ku, Wei Xiong, Dabbu Jaijyan, Hua Zhu, Dai Wang, Jason S McLellan, Ningyan Zhang, Tong-Ming Fu, Zhiqiang An

1383 related Products with: Recognition of a highly conserved glycoprotein B epitope by a bivalent antibody neutralizing HCMV at a post-attachment step.

100ug4 Membranes/Box 100ul100ug Lyophilized4 Membranes/Box100ug100ug Lyophilized100ug Lyophilized100ul100ug Lyophilized100ug Lyophilized100ug

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#32743579   2020/07/22 To Up

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C C Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F Robbiani, Charles M Rice, Michel C Nussenzweig, Theodora Hatziioannou, Paul D Bieniasz

1773 related Products with: Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.

100 0.1 mg100 100 20 ug Product tipe: Antib100 50 ug Product tipe: Antib250ml1000.1 mg25ml100

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#32743578   2020/07/24 To Up

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.

The current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.
Peng Zhao, Jeremy L Praissman, Oliver C Grant, Yongfei Cai, Tianshu Xiao, Katelyn E Rosenbalm, Kazuhiro Aoki, Benjamin P Kellman, Robert Bridger, Dan H Barouch, Melinda A Brindley, Nathan E Lewis, Michael Tiemeyer, Bing Chen, Robert J Woods, Lance Wells

1660 related Products with: Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor.

100 200ug200ug200 0.1 mg200ul1000 1 ml200ul100ul96T

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#32743576   2020/07/20 To Up

design of modular and tunable allosteric biosensors.

Naturally occurring allosteric protein switches have been repurposed for developing novel biosensors and reporters for cellular and clinical applications , but the number of such switches is limited, and engineering them is often challenging as each is different. Here, we show that a very general class of allosteric protein-based biosensors can be created by inverting the flow of information through designed protein switches in which binding of a peptide key triggers biological outputs of interest . Using broadly applicable design principles, we allosterically couple binding of protein analytes of interest to the reconstitution of luciferase activity and a bioluminescent readout through the association of designed lock and key proteins. Because the sensor is based purely on thermodynamic coupling of analyte binding to switch activation, only one target binding domain is required, which simplifies sensor design and allows direct readout in solution. We demonstrate the modularity of this platform by creating biosensors that, with little optimization, sensitively detect the anti-apoptosis protein Bcl-2, the hIgG1 Fc domain, the Her2 receptor, and Botulinum neurotoxin B, as well as biosensors for cardiac Troponin I and an anti-Hepatitis B virus (HBV) antibody that achieve the sub-nanomolar sensitivity necessary to detect clinically relevant concentrations of these molecules. Given the current need for diagnostic tools for tracking COVID-19 , we use the approach to design sensors of antibodies against SARS-CoV-2 protein epitopes and of the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. The latter, which incorporates a designed RBD binder, has a limit of detection of 15pM with an up to seventeen fold increase in luminescence upon addition of RBD. The modularity and sensitivity of the platform should enable the rapid construction of sensors for a wide range of analytes and highlights the power of protein design to create multi-state protein systems with new and useful functions.
Alfredo Quijano-Rubio, Hsien-Wei Yeh, Jooyoung Park, Hansol Lee, Robert A Langan, Scott E Boyken, Marc J Lajoie, Longxing Cao, Cameron M Chow, Marcos C Miranda, Jimin Wi, Hyo Jeong Hong, Lance Stewart, Byung-Ha Oh, David Baker

1442 related Products with: design of modular and tunable allosteric biosensors.

10 mg10 nmol100 mg10 mg100ug2.5 mg1 mg100.00 ul1,000 tests

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#32743570   2020/07/27 To Up

Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV.

A high-resolution understanding of the antibody response to SARS-CoV-2 is important for the design of effective diagnostics, vaccines and therapeutics. However, SARS-CoV-2 antibody epitopes remain largely uncharacterized, and it is unknown whether and how the response may cross-react with related viruses. Here, we use a multiplexed peptide assay ('PepSeq') to generate an epitope-resolved view of reactivity across all human coronaviruses. PepSeq accurately detects SARS-CoV-2 exposure and resolves epitopes across the Spike and Nucleocapsid proteins. Two of these represent recurrent reactivities to conserved, functionally-important sites in the Spike S2 subunit, regions that we show are also targeted for the endemic coronaviruses in pre-pandemic controls. At one of these sites, we demonstrate that the SARS-CoV-2 response strongly and recurrently cross-reacts with the endemic virus hCoV-OC43. Our analyses reveal new diagnostic and therapeutic targets, including a site at which SARS-CoV-2 may recruit common pre-existing antibodies and with the potential for broadly-neutralizing responses.
Jason T Ladner, Sierra N Henson, Annalee S Boyle, Anna L Engelbrektson, Zane W Fink, Fatima Rahee, Jonathan D'ambrozio, Kurt E Schaecher, Mars Stone, Wenjuan Dong, Sanjeet Dadwal, Jianhua Yu, Michael A Caligiuri, Piotr Cieplak, Magnar Bjørås, Mona H Fenstad, Svein A Nordbø, Denis E Kainov, Norihito Muranaka, Mark S Chee, Sergey A Shiryaev, John A Altin

1844 related Products with: Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV.

100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug

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#32743567   2020/07/24 To Up

Immuno-informatics approach for multi-epitope vaccine designing against SARS-CoV-2.

The novel Corona Virus Disease (COVID-19) pandemic has spread a blaze of increasing fatality rates across the world. The dearth of potential vaccines has left the survival of mankind with doubts. The development of multi-epitope vaccine in this current situation could be a possible COVID treatment. We have designed a novel multi-epitope, multi-protein vaccine with different proteins of Severe Acute Respiratory Syndrome - Corona Virus -2 (SARS-CoV-2) with immuno-informatics approaches, which has been validated in silico to be stable and potential. It has been prepared with Cytotoxic T-cell (T) and Helper T-cell (T) binding epitopes overlapping with B-cell binding epitopes predicted for 6 proteins conserved among 4 different viral strains isolated across the world. Both the humoral and cell-mediated immune responses are ensured due to the presence of T cell and B-cell inducing epitopes along with interferon-gamma inducing epitopes present in the vaccine. The final vaccine construct comprises of an adjuvant at the N terminal, Cytotoxic T Lymphocyte and Helper T Lymphocyte epitopes. The construct showed potential antigenicity and was non-allergic. The molecular docking of the refined, validated tertiary structure model of the vaccine was performed with immune-stimulatory Toll Like Receptors (TLR), TLR-2,3,4. The study of binding energetics of the docked complexes revealed binding interactions of receptor with vaccine. The immune simulation of the vaccine even confirmed the initiation of elevated host immune responses. The efficient translation of the vaccine in an expression vector was confirmed with in silico cloning approach. Certainly, the development of such vaccine candidate could possibly be an effective therapy for COVID-19.
Souvik Banerjee, Kaustav Majumder, Gerardo Jose Gutierrez, Debkishore Gupta, Bharti Mittal

2952 related Products with: Immuno-informatics approach for multi-epitope vaccine designing against SARS-CoV-2.

100ug1001 kit(96 Wells)0.5 mg100 mg 500 ml 1000100 100 mg

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#32743537   2020/05/15 To Up

Aspartic acid in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans.

Autoimmune thyroid disease (AITD) is the most common autoimmune disorder worldwide. Remarkably, it is commonly accompanied by other autoimmune diseases, such as rheumatoid arthritis (RA). The immunopathogenic mechanisms behind the coexistence of these disorders are still not completely understood. Immunogenetics influences the physiopathology of these diseases since ethnicity plays an essential role in the inheritance of susceptibility markers.
Luis Francisco Valdés-Corona, Susana Hernández-Doño, Tatiana Sofia Rodríguez-Reyna, Rafael García-Silva, Juan Jakez, Monica Escamilla-Tilch, Guadalupe Lima, Luis Llorente, Carlos Pineda, Edmond Yunis, Julio Granados

1272 related Products with: Aspartic acid in the HLA-DRB1 chain and shared epitope alleles partially explain the high prevalence of autoimmunity in Mexicans.

14 Arrays/Slide96 wells (1 kit)

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#32743535   2020/05/01 To Up

No evidence of autoimmunity to human OX or OX orexin receptors in Pandemrix-vaccinated narcoleptic children.

Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX or OX receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX and OX receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors.
Krister Melén, Pinja Jalkanen, Jyrki P Kukkonen, Markku Partinen, Hanna Nohynek, Arja Vuorela, Outi Vaarala, Tobias L Freitag, Seppo Meri, Ilkka Julkunen

1624 related Products with: No evidence of autoimmunity to human OX or OX orexin receptors in Pandemrix-vaccinated narcoleptic children.

100 μg100 100 μg 10 UG

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