TY  - JOUR
AU  - Bozinovi, Nina
AU  - Ajdačić, Vladimir
AU  - Lazić, Jelena
AU  - Lecerf, Maxime
AU  - Daventure, Victoria
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor M.
AU  - Dimitrov, Jordan D.
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1223
AB  - 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 pi-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.
PB  - Amer Chemical Soc, Washington
T2  - Acs Omega
T1  - Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
EP  - 20458
IS  - 24
SP  - 20450
VL  - 4
DO  - 10.1021/acsomega.9b01548
ER  - 

@article{
author = "Bozinovi, Nina and Ajdačić, Vladimir and Lazić, Jelena and Lecerf, Maxime and Daventure, Victoria and Nikodinović-Runić, Jasmina and Opsenica, Igor M. and Dimitrov, Jordan D.",
year = "2019",
abstract = "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 pi-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.",
publisher = "Amer Chemical Soc, Washington",
journal = "Acs Omega",
title = "Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity",
pages = "20458-20450",
number = "24",
volume = "4",
doi = "10.1021/acsomega.9b01548"
}

Bozinovi, N., Ajdačić, V., Lazić, J., Lecerf, M., Daventure, V., Nikodinović-Runić, J., Opsenica, I. M.,& Dimitrov, J. D.. (2019). Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. in Acs Omega
Amer Chemical Soc, Washington., 4(24), 20450-20458.
https://doi.org/10.1021/acsomega.9b01548

Bozinovi N, Ajdačić V, Lazić J, Lecerf M, Daventure V, Nikodinović-Runić J, Opsenica IM, Dimitrov JD. Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. in Acs Omega. 2019;4(24):20450-20458.
doi:10.1021/acsomega.9b01548 .

Bozinovi, Nina, Ajdačić, Vladimir, Lazić, Jelena, Lecerf, Maxime, Daventure, Victoria, Nikodinović-Runić, Jasmina, Opsenica, Igor M., Dimitrov, Jordan D., "Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity" in Acs Omega, 4, no. 24 (2019):20450-20458,
https://doi.org/10.1021/acsomega.9b01548 . .