Sensitive amperometric immunosensor for pathogen antigen based on MoS2@AuNPs assembling dual-peptide as bioprobes with significant dual signal amplification

Article

Author: Liu, Aihua ; Zheng, Zongmei ; Liu, Junchong ; Liu, Wanjian ; Wang, Mingyang ; Yang, Zhonghuang ; Yu, Haipeng ; Yuan, Jinlong

It is crucial to timely and accurately identify the causative virus for early treatment and urgent prevention. Viral antigen detection can identify those people who are most likely at risk of spreading the disease, but most based on antibodies with limited stability and sensitivity. Peptides offer several advantages over antibodies, such as low cost, smaller size and good stability. The development of electrochemical immunoassay using specific peptide probes have the merits of good sensitivity and selectivity as well as good stability. Herein we report an amperometric immunosensor using peptides as capture probe and recognition probe. The molecular docking suggests that the two peptides of Pi (sequence: NFWISPKLAFALGGGKKKSC) and FK11 (sequence: WFLNDSELISML), bioscreened from phage display, bind to N-terminal domain of SARS-CoV-2 spike protein (SP). The peptide Pi is assembled on MoS₂@AuNPs modified electrode to capture SARS-CoV-2 SP, which is recognized by peptide FK11-displayed phage to form Pi/SARS-CoV-2 SP/FK11-phage sandwich. Then anti-M13 phage conjugated horseradish peroxidase (HRP) (anti M13-HRP) was introduced to recognize the phage capsid protein pVIII to form M13 phage/anti M13-HRP to enrich thousands of HRP, which can further electrochemically catalyze H₂O₂ reduction at highly conductive MoS₂@AuNPs at - 0.35 V. Then amperometric immunosensor was constructed with linear range of 0.1-5000 pg/mL SARS-CoV-2 SP and detection limit of 0.074 pg/mL. The sensor also has good selectivity, batch reproducibility and stability, capable of detecting down to 10 transducing units/mL SARS-CoV-2 pseudoviruses. This work represents the first example of dual-peptide probes based sandwich-type electrochemical immunosensor integrated with dual signal amplification, which may provide a cost-effective assay platform in detecting real SARS-CoV-2 viruses for early diagnosis. The flexible and modular strategy can be extended to develop other type biosensors for a wide range of applications.

01 Dec 2024·Toxicology in Vitro

A high throughput screening assay for human Thyroperoxidase inhibitors

Article

Author: Wade, Michael G ; Friedman, Katie Paul ; Filiatreault, Alain ; Dong, Hongyan ; Wade, Michael G. ; Thomson, Errol M. ; Thomson, Errol M

Rapid, human relevant assays are needed to assess potential hazards of the many chemicals in commerce. An assay of thyroid peroxidase (TPO) inhibition, using the substrate Amplex Ultra Red, was recently adapted for human TPO (AUR-hTPO). We tested a large number (788) of chemicals through this AUR-hTPO assay and compared performance with published results from an assay using enzyme from rat thyroid microsomes (AUR-rTPO). Coded chemicals, from the US EPA ToxCast Inventory, were tested in a tiered approach: 1) Initial screening at a single concentration; 2) Potency estimation for active chemicals with multiple concentrations; 3) Screening active chemicals for the non-specific activity. The assay gave consistent results for positive chemical methimazole and several positive and negative reference chemicals. hTPO inhibition was observed for 190 chemicals reported as positive in rTPO. Of these, 158 showed no confounding activity (interference due to fluorescence or non-specific protein inhibition). Comparison of all result with rTPO data and with evidence of TPO inhibition found in the literature suggest that the current assay has a higher rate of false negative but a much lower rate of false positive compared with the rTPO screen. These findings underscore the effectiveness of the AUR assay, using hTPO enzyme from engineered cell lines, to identify moderate to strong inhibitors but some improvements may be needed to detect weak TPO inhibitors.

01 Apr 2019·Toxicological Sciences

Screening the ToxCast Phase 1, Phase 2, and e1k Chemical Libraries for Inhibitors of Iodothyronine Deiodinases

Article

Author: Denny, Jeffrey S ; Korte, Joseph J ; Knutsen, Carsten N ; Olker, Jennifer H ; Hornung, Michael W ; Hartig, Phillip C ; Degitz, Sigmund J ; Christensen, Jessica P ; Cardon, Mary C ; Kent, Paige M

Deiodinase enzymes play an essential role in converting thyroid hormones between active and inactive forms by deiodinating the pro-hormone thyroxine (T4) to the active hormone triiodothyronine (T3) and modifying T4 and T3 to inactive forms. Chemical inhibition of deiodinase activity has been identified as an important endpoint to include in screening chemicals for thyroid hormone disruption. To address the lack of data regarding chemicals that inhibit the deiodinase enzymes, we developed robust in vitro assays that utilized human deiodinase types 1, 2, and 3 and screened over 1800 unique chemicals from the U.S. EPA's ToxCast phase 1_v2, phase 2, and e1k libraries. Initial testing at a single concentration identified 411 putative deiodinase inhibitors that produced inhibition of 20% or greater in at least 1 of the 3 deiodinase assays, including chemicals that have not previously been shown to inhibit deiodinases. Of these, 228 chemicals produced enzyme inhibition of 50% or greater; these chemicals were further tested in concentration-response to determine relative potency. Comparisons across these deiodinase assays identified 81 chemicals that produced selective inhibition, with 50% inhibition or greater of only 1 of the deiodinases. This set of 3 deiodinase inhibition assays provides a significant contribution toward expanding the limited number of in vitro assays used to identify chemicals with the potential to interfere with thyroid hormone homeostasis. In addition, these results set the groundwork for development and evaluation of structure-activity relationships for deiodinase inhibition, and inform targeted selection of chemicals for further testing to identify adverse outcomes of deiodinase inhibition.

100 Deals associated with FK-011

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	Japan	Fujisawa Pharmaceutical Co., Ltd.	-
Asthma	Phase 2	-	Astellas Pharma, Inc.	-
Asthma	Phase 2	-	Astellas Pharma, Inc.	-
Asthma	Phase 2	Japan	Fujisawa Pharmaceutical Co., Ltd.	-

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