The role of peptide microarrays in biomedical research

Wei, Jianing; Wang, Yaoqi; Zhang, Hua

doi:10.1039/c8ay01442f

Cited by 14 publications

(8 citation statements)

References 102 publications

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“…Alternatively, short antigenic epitopes have emerged as promising substitutes of recombinant proteins in immunoassays. Besides benefiting from well-established peptide chemistry, ease of purification, and high stability, the use of peptide epitopes provides a distinctive capacity to break down heterogeneous immune responses into almost monoclonal antibody specificities, enabling a highly differentiated serological diagnosis. , We have recently reported the discovery of four IgG-specific linear B-cell epitopes that could differentiate SARS-CoV-2 from other coronavirus infections using COVID-19 patients’ plasma samples. , These peptide epitopes are conserved within the circulating COVID-19 variants and thus have the potential to serve as highly specific affinity ligands for improved immunoassay development. In terms of assay formats, classical immunoassays are labor-intensive and require multiple reagents with long incubation, washing, and reaction steps (2–5 h) .…”

mentioning

confidence: 99%

Epitope-Functionalized Gold Nanoparticles for Rapid and Selective Detection of SARS-CoV-2 IgG Antibodies

Lew

Aung

et al. 2021

ACS Nano

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Rapid and inexpensive immunodiagnostic assays to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroconversion are essential for conducting large-scale COVID-19 epidemiological surveillance and profiling humoral responses against SARS-CoV-2 infections or immunizations. Herein, a colorimetic serological assay to detect SARS-CoV-2 IgGs in patients’ plasma was developed using short antigenic epitopes conjugated to gold nanoparticles (AuNPs). Four immunodominant linear B-cell epitopes, located on the spike (S) and nucleocapsid (N) proteins of SARS-CoV-2, were characterized for their IgG binding affinity and used as highly specific biological motifs on the nanoparticle to recognize target antibodies. Specific bivalent binding between SARS-CoV-2 antibodies and epitope-functionalized AuNPs trigger nanoparticle aggregation, which manifests as a distinct optical transition in the AuNPs’ plasmon characteristics within 30 min of antibody introduction. Co-immobilization of two epitopes improved the assay sensitivity relative to single-epitope AuNPs with a limit of detection of 3.2 nM, commensurate with IgG levels in convalescent COVID-19-infected patients. A passivation strategy was further pursued to preserve the sensing response in human plasma medium. When tested against 35 clinical plasma samples of varying illness severity, the optimized nanosensor assay can successfully identify SARS-CoV-2 infection with 100% specificity and 83% sensitivity. As the epitopes are conserved within the circulating COVID-19 variants, the proposed platform holds great potential to serve as a cost-effective and highly specific alternative to classical immunoassays employing recombinant viral proteins. These epitope-enabled nanosensors further expand the serodiagnostic toolbox for COVID-19 epidemiological study, humoral response monitoring, or vaccine efficiency assessment.

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mentioning

confidence: 99%

Epitope-Functionalized Gold Nanoparticles for Rapid and Selective Detection of SARS-CoV-2 IgG Antibodies

Lew

Aung

et al. 2021

ACS Nano

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“…To address this issue and to facilitate high-throughput assessment of molecular interactions between venom toxin epitopes and antivenom antibody paratopes, high-density peptide microarray (hdpm) technology has recently been adapted to the field of toxinology [13][14][15]. Hdpms have long been successfully applied to a range of fields, such as enzyme inhibition, immunoassays, affinity agents for viruses, and therapeutic peptides amongst others [16]. However, the application of this technology to venom and antivenom research is relatively new [13].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity

et al. 2020

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Snakebite envenoming is a major neglected tropical disease that affects millions of people every year. The only effective treatment against snakebite envenoming consists of unspecified cocktails of polyclonal antibodies purified from the plasma of immunized production animals. Currently, little data exists on the molecular interactions between venom-toxin epitopes and antivenom-antibody paratopes. To address this issue, high-density peptide microarray (hdpm) technology has recently been adapted to the field of toxinology. However, analysis of such valuable datasets requires expert understanding and, thus, complicates its broad application within the field. In the present study, we developed a userfriendly, and high-throughput web application named "Snake Toxin and Antivenom Binding Profiles" (STAB Profiles), to allow straightforward analysis of hdpm datasets. To test our tool and evaluate its performance with a large dataset, we conducted hdpm assays using all African snake toxin protein sequences available in the UniProt database at the time of study design, together with eight commercial antivenoms in clinical use in Africa, thus representing the largest venom-antivenom dataset to date. Furthermore, we introduced a novel method for evaluating raw signals from a peptide microarray experiment and a data normalization protocol enabling intra-microarray and even inter-microarray chip comparisons. Finally, these data, alongside all the data from previous similar studies by Engmark et al., were preprocessed according to our newly developed protocol and made publicly available for download through the STAB Profiles web application (http://tropicalpharmacology.com/ tools/stab-profiles/). With these data and our tool, we were able to gain key insights into toxin-antivenom interactions and were able to differentiate the ability of different antivenoms to interact with certain toxins of interest.

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“…Synthetic peptides mimicking the antigenic determinants of full protein antigens and acting as their minimized surrogates, offer new opportunities for the development of immunoprobes with superior characteristics in terms of ease of handling, reproducibility, costs and stability in the typical low resource setting conditions (for example storage at high humidity at RT) [11,12,13].…”

Section: Introductionmentioning

confidence: 99%

Computational Analysis of Dengue Virus Envelope Protein (E) Reveals an Epitope with Flavivirus Immunodiagnostic Potential in Peptide Microarrays

Bergamaschi

Fassi

Romanato

et al. 2019

IJMS

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The mosquito-borne viral disease caused by the Dengue virus is an expanding global threat. Diagnosis in low-resource-settings and epidemiological surveillance urgently requires new immunoprobes for serological tests. Structure-based epitope prediction is an efficient method to design diagnostic peptidic probes able to reveal specific antibodies elicited in response to infections in patients’ sera. In this study, we focused on the Dengue viral envelope protein (E); computational analyses ranging from extensive Molecular Dynamics (MD) simulations and energy-decomposition-based prediction of potentially immunoreactive regions identified putative epitope sequences. Interestingly, one such epitope showed internal dynamic and energetic properties markedly different from those of other predicted sequences. The epitope was thus synthesized as a linear peptide, modified for chemoselective immobilization on microarrays and used in a serological assay to discriminate Dengue-infected individuals from healthy controls. The synthetic epitope probe showed a diagnostic performance comparable to that of the full antigen in terms of specificity and sensitivity. Given the high level of sequence identity among different flaviviruses, the epitope was immune-reactive towards Zika-infected sera as well. The results are discussed in the context of the quest for new possible structure-dynamics-based rules for the prediction of the immunoreactivity of selected antigenic regions with potential pan-flavivirus immunodiagnostic capacity.

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The role of peptide microarrays in biomedical research

Abstract: Peptide microarrays, comprising hundreds to thousands of different peptides on solid supports in a spatially discrete pattern, are increasingly being used as high throughput screening tools with high sensitivity in biomedical science.

Cited by 14 publications

References 102 publications

Epitope-Functionalized Gold Nanoparticles for Rapid and Selective Detection of SARS-CoV-2 IgG Antibodies

Epitope-Functionalized Gold Nanoparticles for Rapid and Selective Detection of SARS-CoV-2 IgG Antibodies

An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity

Computational Analysis of Dengue Virus Envelope Protein (E) Reveals an Epitope with Flavivirus Immunodiagnostic Potential in Peptide Microarrays

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