Synthetic Haptens and Monoclonal Antibodies to the Cyanotoxin Anatoxin‐a

Quiñones-Reyes, Guillermo; Agulló, Consuelo; Mercader, Josep V.; Abad‐Somovilla, Antonio; Abad‐Fuentes, Antonio

doi:10.1002/anie.201904002

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…For over a century, antibodies have been widely and successfully utilized in biomedicine, biochemistry, and bioanalysis. − Antibodies are glycoproteins derived from the humoral immune system that naturally respond to macromolecules such as bacteria, viruses, and proteins. In the case of low-molecular-weight compounds (<1000 Da), such as pharmaceuticals, poisons, and drugs of abuse, these small molecules cannot be effectively recognized by the immune system to induce a subsequent antibody response. , To produce antibodies against small molecules, structural analogs of targets, named haptens, should be conjugated to larger molecules, called carriers. As well-established biological reagents, thousands of antibodies against small molecules with varied titers and affinities have been produced .…”

Section: Introductionmentioning

confidence: 99%

Influence of Small Molecular Property on Antibody Response

Wen

Bai

Wei

et al. 2020

J. Agric. Food Chem.

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Antibodies with high titer and affinity to small molecule are critical in the field for the development of vaccines against drugs of abuse, antidotes to toxins and immunoassays for compounds. However, little is known regarding how properties of small molecule per se influence and which chemical descriptor could indicate the degree of the antibody response. Based on our previous study, we designed and synthesized two groups of small molecules, called haptens, with varied hydrophobicities to investigate the relationship between properties of small molecules and antibody response in term of titer and affinity. We found that the magnitude of the antibody response is positively correlated with the degree of molecular hydrophobicity and related chemical descriptors. This study provides insight into the immunological characteristics of small molecules themselves and useful clues to produce high-quality antibodies against small molecules.

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Section: Introductionmentioning

confidence: 99%

Influence of Small Molecular Property on Antibody Response

Wen

Bai

Wei

et al. 2020

J. Agric. Food Chem.

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“…Patulin monitoring by antibody-based rapid methods is a long-standing goal in food immunodiagnostics, but the small size of the molecule together with its high electrophilic reactivity makes the aim of obtaining suitable antibodies certainly a challenge. Common knowledge in the field of immunoanalytical methods to haptens advices that the functionalized immunizing derivative should closely mimic the conformation, main chemical groups, and electronic distribution of the target molecule 20 , 21 . Accordingly, previous attempts have tried to adhere strictly to this general rule.…”

Section: Resultsmentioning

confidence: 99%

Chemical strategies for triggering the immune response to the mycotoxin patulin

Duncan

Mercader

Agulló

et al. 2021

Sci Rep

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Mycotoxins represent a major concern for human and animal health because of their harmful effects and high occurrence in food and feed. Rapid immunoanalytical methods greatly contribute to strengthening the safety of our food supply by efficiently monitoring chemical contaminants, so high-affinity and specific antibodies have been generated for almost all internationally regulated mycotoxins. The only exception is patulin, a mycotoxin mainly produced by Penicillium expansum for which such a target has not yet been achieved. Accordingly, no point-of-need tests commonly used in food immunodiagnostics are commercially available for patulin. In the present study, three functionalized derivatives conforming to generally accepted rules in hapten design were firstly tested to generate suitable antibodies for the sensitive immunodetection of patulin. However, these conventional bioconjugates were unable to elicit the desired immune response, so an alternative strategy that takes advantage of the high electrophilic reactivity of patulin was explored. Patulin was reacted with 4-bromothiophenol, and the obtained adduct was used to produce antibodies with nanomolar affinity values. These results demonstrated for the first time that targeting the adduct resulting from the reaction of patulin with a thiol-containing compound is a promising approach for developing user-friendly immunoanalytical techniques for this elusive mycotoxin.

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“…Therefore, hapten design and synthesis are widely regarded as critical steps in the development of antibody-based techniques for the detection of chemical contaminants. In particular, the position of the spacer arm on the target molecule has been revealed to be of the utmost importance for the generation of antibodies with the desired affinity and specificity [ 2 ]. Nevertheless, predicting the optimum linker tethering site is frequently difficult.…”

Section: Introductionmentioning

confidence: 99%

Alternative Hapten Design for Zearalenone Immunoreagent Generation

Abad‐Fuentes

Agulló

López-Puertollano

et al. 2022

Toxins

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Appropriate hapten design and synthesis have been identified as critical steps to generate high-performance immunoreagents and to develop sensitive and selective immunoanalytical methods. Antibodies and immunoassays for the major mycotoxin zearalenone have been reported and marketed. However, zearalenone haptens have mostly been prepared by the oxime active ester technique, and hapten characterization has generally been poor or non-existent. In the present study, novel haptens of zearalenone with longer linkers and with alternative tethering sites have been designed for immunizing and assay conjugate preparation. All of these molecules were purified and spectroscopically verified, and a structure-activity relationship evaluation was carried out. This approach revealed that the hapten with the linker at the carbonyl group generated antibodies with a higher affinity than the hapten functionalized at the phenyl moiety. Antibodies produced with the latter hapten, on the other hand, showed lower cross-reactivity values to the major zearalenone metabolites. Finally, similar immunoassay sensitivity was achieved with all of the antibodies when heterologous haptens were employed. Furthermore, by altering the structure of the competing antigen, the immunoassay selectivity was modified. These results demonstrate that immunochemical methods for zearalenone rapid analysis can still be improved in terms of sensitivity and selectivity.

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Synthetic Haptens and Monoclonal Antibodies to the Cyanotoxin Anatoxin‐a

Cited by 21 publications

References 29 publications

Influence of Small Molecular Property on Antibody Response

Influence of Small Molecular Property on Antibody Response

Chemical strategies for triggering the immune response to the mycotoxin patulin

Alternative Hapten Design for Zearalenone Immunoreagent Generation

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