Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
Аутори
Bozinovi, NinaAjdačić, Vladimir
Lazić, Jelena
Lecerf, Maxime
Daventure, Victoria
Nikodinović-Runić, Jasmina
Opsenica, Igor M.
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 pi-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:
- Amer Chemical Soc, Washington
Финансирање / пројекти:
- European Research Council [ERC-StG-678905 CoBABATI]
- INSERM
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-MESTD-Basic Research (BR or ON)-172008)
- PHC French-Serbian partnership project Pavle Savic [451-03-01963/2017-09/03]
DOI: 10.1021/acsomega.9b01548
ISSN: 2470-1343
WoS: 000502130800005
Scopus: 2-s2.0-85075681500
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .