The Experts below are selected from a list of 159 Experts worldwide ranked by ideXlab platform
Jeong Woo Choi - One of the best experts on this subject based on the ideXlab platform.
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Multi-electroChemical signal generation using metalloprotein based on selective surface modification
BioChip Journal, 2017Co-Authors: Yong-ho Chung, Junhong Min, Si-youl Yoo, Jinho Yoon, Jeong Woo ChoiAbstract:In this research, we demonstrate a simple method to generate a multi-peak in a single electroChemical signal for the application to bioelectronics devices. Myoglobin is used as a source of electroChemical signal, and its property of redox peak is controlled by the introduction of various Chemical-linking materials. Based on controlled signals of myoglobin, multisignal having dual peak is achieved by the signal combination of six electrodes, which have different electroChemical signals by the modification of each electrode with different kinds of Chemical Linkers individually. For the device formation, selective immobilization process was performed by using reductive cleavage of pre-immobilized thiol group. As a result, the proposed concept shows simple and effective formation of a multi-signal in a single electroChemical signal as compared with other methods based on heterolayer and hybrid materials, and it can be directly applied to materialize practical bioelectronic devices such as a bio-logic gate or bio-computing system
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Multi-Functional Biomemory Device Composed of Recombinant Metalloprotein
Advanced Materials Research, 2013Co-Authors: Jeong Woo ChoiAbstract:We developed a multi-functional biomemory device composed of cytochrome c and recombinant azurins which have different metal ions in the core. Azurin, one of the well-known metalloproteins, was modified by attaching cysteine residue containing thiol functional group for direct immobilization without Chemical Linkers. The immobilization of metalloproteins was confirmed by atomic force microscopy (AFM) and surface plasmon resonance (SPR) spectroscopy. The redox properties of immobilized recombinant azurin were validated with cyclic voltammetry (CV), and memory functions using various metalloprotein structures were confirmed by the technique of open circuit potential amperometry (OCPA). We achieved various practical functions based on basic memory functions including write, erase, and read using recombinant azurin and other metalloproteins, and this proposed multifunctional biodevice could be directly applied to the realization of bioelectronics device for next generation, such as single molecular functional device, bioprocessor and biocomputing system.
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Investigation of the redox property of a metalloprotein layer self-assembled on various Chemical Linkers.
Colloids and surfaces. B Biointerfaces, 2011Co-Authors: Yong-ho Chung, Taek Lee, Junhong Min, Jeong Woo ChoiAbstract:Myogloblin, a well-known metalloprotein, was immobilized on a gold surface using various Chemical Linkers to investigate the length effect of Chemical linker on the electron transfer in protein layers, because Chemical Linkers play roles in the pathway that transfers the electron from the protein to the gold substrate and act as protein immobilization reagents. Chemical Linkers with 2, 6, 11, and 16 carbons were utilized to confirm length-effects. The immobilization of protein and Chemical linker was validated with surface plasmon resonance (SPR) and atomic force microscopy (AFM). The electroChemical property was evaluated by cyclic voltammetry (CV) and chronocoulometry (CC). In those results, redox peaks of immobilized protein were controlled via the length of Chemical Linkers, and it could be directly applied to the realization of bioelectronic device.
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Investigation of the redox property of a metalloprotein layer self-assembled on various Chemical Linkers B Biointerfaces
Colloids and Surfaces, 2011Co-Authors: Yong-ho Chung, Junhong Min, Taek Sung Lee, Jeong Woo ChoiAbstract:Myogloblin, a well-known metalloprotein, was immobilized on a gold surface using various Chemical Linkers to investigate the length effect of Chemical linker on the electron transfer in protein layers, because Chemical Linkers play roles in the pathway that transfers the electron from the protein to the gold substrate and act as protein immobilization reagents. Chemical Linkers with 2, 6, 11, and 16 carbons were utilized to confirm length-effects. The immobilization of protein and Chemical linker was validated with surface plasmon resonance (SPR) and atomic force microscopy (AFM). The electroChemical property was evaluated by cyclic voltammetry (CV) and chronocoulometry (CC). In those results, redox peaks of immobilized protein were controlled via the length of Chemical Linkers, and it could be directly applied to the realization of bioelectronic device.
Elías Pérez - One of the best experts on this subject based on the ideXlab platform.
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Fluorescence tuning of confined molecules in porous silicon mirrors
Applied Physics Letters, 2007Co-Authors: Gabriela Palestino, J. A. Del Río, Csilla Gergely, M.b. De La Mora, Elías PérezAbstract:Emission signal from fluorescent molecules fluorescein-5-maleimide in a porous silicon mirror is enhanced by tuning the pore size and reflectance spectrum of the porous silicon multilayer structure. This is achieved when the reflectance spectrum of the silicon mirror overlaps the fluorescent excitation and emission wavelengths of the fluorescent molecule, and Chemical Linkers assure the molecular confinement.
Yong-ho Chung - One of the best experts on this subject based on the ideXlab platform.
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Multi-electroChemical signal generation using metalloprotein based on selective surface modification
BioChip Journal, 2017Co-Authors: Yong-ho Chung, Junhong Min, Si-youl Yoo, Jinho Yoon, Jeong Woo ChoiAbstract:In this research, we demonstrate a simple method to generate a multi-peak in a single electroChemical signal for the application to bioelectronics devices. Myoglobin is used as a source of electroChemical signal, and its property of redox peak is controlled by the introduction of various Chemical-linking materials. Based on controlled signals of myoglobin, multisignal having dual peak is achieved by the signal combination of six electrodes, which have different electroChemical signals by the modification of each electrode with different kinds of Chemical Linkers individually. For the device formation, selective immobilization process was performed by using reductive cleavage of pre-immobilized thiol group. As a result, the proposed concept shows simple and effective formation of a multi-signal in a single electroChemical signal as compared with other methods based on heterolayer and hybrid materials, and it can be directly applied to materialize practical bioelectronic devices such as a bio-logic gate or bio-computing system
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Investigation of the redox property of a metalloprotein layer self-assembled on various Chemical Linkers.
Colloids and surfaces. B Biointerfaces, 2011Co-Authors: Yong-ho Chung, Taek Lee, Junhong Min, Jeong Woo ChoiAbstract:Myogloblin, a well-known metalloprotein, was immobilized on a gold surface using various Chemical Linkers to investigate the length effect of Chemical linker on the electron transfer in protein layers, because Chemical Linkers play roles in the pathway that transfers the electron from the protein to the gold substrate and act as protein immobilization reagents. Chemical Linkers with 2, 6, 11, and 16 carbons were utilized to confirm length-effects. The immobilization of protein and Chemical linker was validated with surface plasmon resonance (SPR) and atomic force microscopy (AFM). The electroChemical property was evaluated by cyclic voltammetry (CV) and chronocoulometry (CC). In those results, redox peaks of immobilized protein were controlled via the length of Chemical Linkers, and it could be directly applied to the realization of bioelectronic device.
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Investigation of the redox property of a metalloprotein layer self-assembled on various Chemical Linkers B Biointerfaces
Colloids and Surfaces, 2011Co-Authors: Yong-ho Chung, Junhong Min, Taek Sung Lee, Jeong Woo ChoiAbstract:Myogloblin, a well-known metalloprotein, was immobilized on a gold surface using various Chemical Linkers to investigate the length effect of Chemical linker on the electron transfer in protein layers, because Chemical Linkers play roles in the pathway that transfers the electron from the protein to the gold substrate and act as protein immobilization reagents. Chemical Linkers with 2, 6, 11, and 16 carbons were utilized to confirm length-effects. The immobilization of protein and Chemical linker was validated with surface plasmon resonance (SPR) and atomic force microscopy (AFM). The electroChemical property was evaluated by cyclic voltammetry (CV) and chronocoulometry (CC). In those results, redox peaks of immobilized protein were controlled via the length of Chemical Linkers, and it could be directly applied to the realization of bioelectronic device.
Gabriela Palestino - One of the best experts on this subject based on the ideXlab platform.
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Fluorescence tuning of confined molecules in porous silicon mirrors
Applied Physics Letters, 2007Co-Authors: Gabriela Palestino, J. A. Del Río, Csilla Gergely, M.b. De La Mora, Elías PérezAbstract:Emission signal from fluorescent molecules fluorescein-5-maleimide in a porous silicon mirror is enhanced by tuning the pore size and reflectance spectrum of the porous silicon multilayer structure. This is achieved when the reflectance spectrum of the silicon mirror overlaps the fluorescent excitation and emission wavelengths of the fluorescent molecule, and Chemical Linkers assure the molecular confinement.
Kristi Elkins - One of the best experts on this subject based on the ideXlab platform.
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in vivo effects of targeting cd79b with antibodies and antibody drug conjugates
Molecular Cancer Therapeutics, 2009Co-Authors: Bing Zheng, Shang-fan Yu, Kristi Elkins, Katherine R Kozak, Reina N Fuji, Josefa Chuh, Jo Anne Hongo, Helga Raab, Marna Williams, Elena McdormanAbstract:Antibodies directed against B cells are in use for the treatment of non-Hodgkin's lymphoma and autoimmune disorders. The B-cell–restricted surface antigen CD79b, a signaling component of the B-cell receptor, has been shown as a promising antibody target in mouse efficacy models of systemic lupus erythematosus. Anti-CD79b antibody-drug conjugates (ADC), cytotoxic drugs linked through specialized Chemical Linkers to antibodies, are effective in mouse xenograft models of non-Hodgkin's lymphoma. We were interested in evaluating the systemic effects of anti-CD79b antibodies and ADCs in normal animals as a step toward the development of these molecules as therapeutics. As we were unable to identify any cell surface binding anti-human CD79b antibodies that were cross-reactive to other species, we developed an antibody to cynomolgus monkey ( Macaca fascicularis ) CD79b (anti-cyCD79b). The anti-cynomolgus antibody, anti-cyCD79b (10D10), and the maytansine (tubulin inhibitor)–conjugated ADC, anti-cyCD79b (10D10)-MCC-DM1, were administered to cynomolgus monkeys at ∼30 mg/kg (6,000 μg DM1/m2) for two doses 3 weeks apart. Anti-cyCD79b and anti-cyCD79b-MCC-DM1 resulted in peripheral blood B-cell depletion of ∼65% and ∼94%, respectively. In addition, anti-cyCD79b-MCC-DM1 resulted in near-complete absence of splenic germinal centers, an observation supporting an effect on dividing B cells. Both molecules were well tolerated, with minimal findings for the antibody and findings for the ADC limited to the lymphoid and hematopoietic systems, liver, and peripheral nerves. These preclinical data suggest that targeting CD79b with antibodies or ADCs may provide safe and effective therapies for B-cell malignancies and autoimmune diseases. [Mol Cancer Ther 2009;8(10):2937–46]
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antibody drug conjugates for the treatment of non hodgkin s lymphoma target and linker drug selection
Cancer Research, 2009Co-Authors: Andrew Polson, Kristi Elkins, Dan L Eaton, Jill Caleminefenaux, Pamela Chan, Wesley Chang, Erin H Christensen, Suzanna Clark, Frederic J De Sauvage, Michael J ElliottAbstract:Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via Chemical Linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. Here, we systematically examine the potential targets and linker-drug combinations that could provide an optimal ADC for the treatment for non-Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, and CD180) for potential treatment of non-Hodgkin's lymphoma with ADCs. ADCs with cleavable Linkers mediated in vivo efficacy via all these targets; ADCs with uncleavable Linkers were only effective when targeted to CD22 and CD79b. In target-independent safety studies in rats, the uncleavable linker ADCs showed reduced toxicity, presumably due to the reduced release of free drug or other toxic metabolites into the circulation. Thus, our data suggest that ADCs with cleavable Linkers work on a broad range of targets, and for specific targets, ADCs with uncleavable Linkers provide a promising opportunity to improve the therapeutic window for ADCs in humans.
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development and therapeutic potential of an anti cd79b antibody drug conjugate anti cd79b vc mmae for the treatment of non hodgkin s lymphoma
Blood, 2008Co-Authors: Andrew Polson, Kristi Elkins, Fiona Bennett, Mark S Dennis, Dan L Eaton, Allen Ebens, Dorothy French, Mary Ann T Go, Yvonne Chen, Andrew JackAbstract:Antibody-drug conjugates (ADCs), antibodies linked to potent cytotoxic drugs via specialized Chemical Linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. We have previously shown that ADCs targeted to CD79b are highly effective in xenograft models of non-Hodgkin’s lymphoma. Here we report the development of an ADC consisting of a humanized anti-CD79b antibody (hu-anti-CD79b) conjugated to monomethylauristatin E (MMAE) through engineered cysteines (THIOMABS) by a maleimidocaproyl-valinecitrulline-p-aminobenzyloxycarbonyl (MC-vcPAB) linker (hu-anti-CD79b-thioMAb-MC-vc-PAB-MMAE) that is designed to be cleaved by cathepsins. To determine the potential of this ADC, hu-anti-CD79b-thioMAb-MC-vc-PAB-MMAE (referred to as anti-CD79b-vcMMAE henceforth), as a therapeutic for NHL we interrogated its potency across a large panel of NHL cell lines. Strikingly, anti-CD79b-vcMMAE has very potent activity across a large panel of NHL cell lines in vitro with 68% (23 out of 34) cell lines having greater than 50% reduction in cell viability. Quantitative FACS across the cell line panel revealed that of the 11 insensitive cell lines, 9 had negligible surface CD79b, suggesting a threshold effect in that below a specific level of antigen on the cell surface resulted in cells being insensitive to anti-CD79b-vcMMAE. Within the sensitive cell lines, there was not a direct correlation per se with anti-CD79b-vcMMAE IC50 values and cell surface expression levels and this prompted us to investigate other potential molecular parameters. Gene expression profiling and gene set enrichment analysis revealed that genes predominantly involved in antigen processing and presentation and genes induced by IFN-gamma were significantly enriched in the less sensitive cell lines to CD79b-vcMMAE. Classifying our NHL cell lines as GCB or ABC subtypes by gene expression revealed that both ABC and GCB were responsive. In addition, the activity of anti-CD79b-vcMMAE was very potent in p53 mutant as well as p53 wild-type cell lines. Since the pre-clinical evidence suggests that anti-CD79b-vcMMAE will be a very promising drug candidate for NHL and we have established that cell surface expression is perhaps the best predictor of response, we wished to determine the prevalence of expression of CD79b on the cell surface of primary human lymphoma and CLL samples to estimate a patient population that may gain benefit. Strikingly, CD79b was detected in all cases of CLL, MZL, HCL, DLBCL, FL, and MCL. Furthermore, CD79b expression was detected in all cases that had relapsed from prior chemotherapy regimens, highlighting the clinical relevance of this target and potential therapeutic utility of anti-CD79b-vcMMAE. To assess the potential of anti-CD79b-vcMMAE in vivo we compared its efficacy to R-CHOP in three xenograft models of NHL. In all three models, a single dose of anti-CD79b-vcMMAE resulted in complete sustained tumor remission and was more effective than R-CHOP. These data suggest that anti-CD79b-vcMMAE could be broadly efficacious as a treatment for NHL.