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Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
- Source :
- ACS Omega, ACS Omega, 2019, 4 (24), pp.20450-20458. ⟨10.1021/acsomega.9b01548⟩, ACS Omega, ACS Publications, 2019, 4 (24), pp.20450-20458. ⟨10.1021/acsomega.9b01548⟩, ACS Omega, Vol 4, Iss 24, Pp 20450-20458 (2019)
- Publication Year :
- 2019
- Publisher :
- American Chemical Society, 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. Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3794]
- Subjects :
- Heme binding
[SDV.IMM] Life Sciences [q-bio]/Immunology
General Chemical Engineering
[SDV]Life Sciences [q-bio]
Cofactor
Article
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antigen
Chloroquine
[CHIM] Chemical Sciences
medicine
[CHIM]Chemical Sciences
Heme
QD1-999
030304 developmental biology
0303 health sciences
biology
General Chemistry
Porphyrin
3. Good health
[SDV] Life Sciences [q-bio]
Chemistry
chemistry
Biochemistry
[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology
Biological significance
030220 oncology & carcinogenesis
[SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology
biology.protein
[SDV.IMM]Life Sciences [q-bio]/Immunology
Antibody
medicine.drug
Subjects
Details
- ISSN :
- 24701343
- Database :
- OpenAIRE
- Journal :
- ACS Omega, ACS Omega, 2019, 4 (24), pp.20450-20458. ⟨10.1021/acsomega.9b01548⟩, ACS Omega, ACS Publications, 2019, 4 (24), pp.20450-20458. ⟨10.1021/acsomega.9b01548⟩, ACS Omega, Vol 4, Iss 24, Pp 20450-20458 (2019)
- Accession number :
- edsair.doi.dedup.....ded30fcdaa8d406d9937f1a69e37eeb0