Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
Аутори
Božinović, Nina S.Ajdačić, Vladimir
Lazić, Jelena O.
Lecerf, Maxime
Daventure, Victoria
Nikodinović-Runić, Jasmina
Opsenica, Igor
Dimitrov, Jordan D.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 antibod...y 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.
Извор:
ACS Omega, 2019, 4, 24, 20450-20458Издавач:
- American Chemical Society
Финансирање / пројекти:
- European Research Council (grant ERC-StG-678905 CoBABATI to J.D.D.)
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-172008)
- PHC French-Serbian partnership project Pavle Savić (451-03- 01963/2017-09/03)
Напомена:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3794
DOI: 10.1021/acsomega.9b01548
ISSN: 2470-1343
WoS: 000502130800005
Scopus: 2-s2.0-85075681500
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Božinović, Nina S. AU - Ajdačić, Vladimir AU - Lazić, Jelena O. AU - Lecerf, Maxime AU - Daventure, Victoria AU - Nikodinović-Runić, Jasmina AU - Opsenica, Igor AU - Dimitrov, Jordan D. PY - 2019 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3793 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 π-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes. PB - American Chemical Society T2 - ACS Omega T1 - Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity VL - 4 IS - 24 SP - 20450 EP - 20458 DO - 10.1021/acsomega.9b01548 ER -
@article{ author = "Božinović, Nina S. and Ajdačić, Vladimir and Lazić, Jelena O. and Lecerf, Maxime and Daventure, Victoria and Nikodinović-Runić, Jasmina and Opsenica, Igor 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 π-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.", publisher = "American Chemical Society", journal = "ACS Omega", title = "Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity", volume = "4", number = "24", pages = "20450-20458", doi = "10.1021/acsomega.9b01548" }
Božinović, N. S., Ajdačić, V., Lazić, J. O., Lecerf, M., Daventure, V., Nikodinović-Runić, J., Opsenica, I.,& Dimitrov, J. D.. (2019). Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. in ACS Omega American Chemical Society., 4(24), 20450-20458. https://doi.org/10.1021/acsomega.9b01548
Božinović NS, Ajdačić V, Lazić JO, Lecerf M, Daventure V, Nikodinović-Runić J, Opsenica I, 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 .
Božinović, Nina S., Ajdačić, Vladimir, Lazić, Jelena O., Lecerf, Maxime, Daventure, Victoria, Nikodinović-Runić, Jasmina, Opsenica, Igor, 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 . .