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Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity

[Image: see text] In a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreacti...

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Autores principales: Božinović, Nina, Ajdačić, Vladimir, Lazic, Jelena, Lecerf, Maxime, Daventure, Victoria, Nikodinovic-Runic, Jasmina, Opsenica, Igor M., Dimitrov, Jordan D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906781/
https://www.ncbi.nlm.nih.gov/pubmed/31858028
http://dx.doi.org/10.1021/acsomega.9b01548
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author Božinović, Nina
Ajdačić, Vladimir
Lazic, Jelena
Lecerf, Maxime
Daventure, Victoria
Nikodinovic-Runic, Jasmina
Opsenica, Igor M.
Dimitrov, Jordan D.
author_facet Božinović, Nina
Ajdačić, Vladimir
Lazic, Jelena
Lecerf, Maxime
Daventure, Victoria
Nikodinovic-Runic, Jasmina
Opsenica, Igor M.
Dimitrov, Jordan D.
author_sort Božinović, Nina
collection PubMed
description [Image: see text] In a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreactivity upon exposure to porphyrin cofactor heme. Molecular mechanisms and biological significance of the appearance of cryptic polyreactivity are not well understood. It is believed that heme acts as an interfacial cofactor between the antibody and the newly recognized antigens. To further test this claim and gain insight into the types of interactions involved in heme binding, we herein investigated the influence of a group of aromatic guanylhydrazone molecules on the heme-induced antibody polyreactivity. From the analysis of SAR and the results of UV–vis absorbance spectroscopy, it was concluded that the most probable mechanism by which the studied molecules inhibit heme-mediated polyreactivity of the antibody is the direct binding to heme, thus preventing heme from binding to antibody and/or antigen. The inhibitory capacity of the most potent compounds was substantially higher than that of chloroquine, a well-known heme binder. Some of the guanylhydrazone molecules were able to induce polyreactivity of the studied antibody themselves, possibly by a mechanism similar to heme. Results described here point to the conclusion that heme indeed must bind to an antibody to induce its polyreactivity, and that both π-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.
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spelling pubmed-69067812019-12-19 Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity Božinović, Nina Ajdačić, Vladimir Lazic, Jelena Lecerf, Maxime Daventure, Victoria Nikodinovic-Runic, Jasmina Opsenica, Igor M. Dimitrov, Jordan D. ACS Omega [Image: see text] In a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreactivity upon exposure to porphyrin cofactor heme. Molecular mechanisms and biological significance of the appearance of cryptic polyreactivity are not well understood. It is believed that heme acts as an interfacial cofactor between the antibody and the newly recognized antigens. To further test this claim and gain insight into the types of interactions involved in heme binding, we herein investigated the influence of a group of aromatic guanylhydrazone molecules on the heme-induced antibody polyreactivity. From the analysis of SAR and the results of UV–vis absorbance spectroscopy, it was concluded that the most probable mechanism by which the studied molecules inhibit heme-mediated polyreactivity of the antibody is the direct binding to heme, thus preventing heme from binding to antibody and/or antigen. The inhibitory capacity of the most potent compounds was substantially higher than that of chloroquine, a well-known heme binder. Some of the guanylhydrazone molecules were able to induce polyreactivity of the studied antibody themselves, possibly by a mechanism similar to heme. Results described here point to the conclusion that heme indeed must bind to an antibody to induce its polyreactivity, and that both π-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes. American Chemical Society 2019-11-22 /pmc/articles/PMC6906781/ /pubmed/31858028 http://dx.doi.org/10.1021/acsomega.9b01548 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Božinović, Nina
Ajdačić, Vladimir
Lazic, Jelena
Lecerf, Maxime
Daventure, Victoria
Nikodinovic-Runic, Jasmina
Opsenica, Igor M.
Dimitrov, Jordan D.
Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title_full Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title_fullStr Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title_full_unstemmed Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title_short Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
title_sort aromatic guanylhydrazones for the control of heme-induced antibody polyreactivity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906781/
https://www.ncbi.nlm.nih.gov/pubmed/31858028
http://dx.doi.org/10.1021/acsomega.9b01548
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