Abstract: SA-PO829
The High-Throughput Approach Identifies Compounds that Block PLA2R and Anti-PLA2R Antibody Interaction
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - III
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Feng, Zixin, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
- Guo, Fusheng, Peking University College of Chemistry and Molecular Engineering, Beijing, Beijing, China
- Cui, Zhao, Peking University First Hospital Department of Nephrology Renal Division, Beijing, China
Background
The pathogenicity of anti-phospholipase A2 receptor (PLA2R) antibodies has been elucidated in primary membranous nephropathy (MN).
Methods
Small-molecule compounds were screened for their inhibition effects to the binding between PLA2R and its antibodies by ELISA. The affinity of anti-PLA2R antibodies from MN patients to the full-length extracellular PLA2R was determined by surface plasmon resonance (SPR). The blocking ability of each compound was tested by SPR competition study. The affinity of each compound was determined by SPR.
Results
15 candidate compounds were selected from a library of over 4,000 small-molecule compounds for their inhibition rates > 20% to the binding between PLA2R and its antibodies. The affinity of anti-PLA2R antibodies and PLA2R antigens was similar among patients as approximately 1.0nM. The inhibitory potential of the 15 candidates was assessed by SPR and three compounds, Macrocarpal B, Doramectin, and Hypocrellin exhibit reproducible inhibitory ability, with Macrocarpal B being the most significant one. Macrocarpal B could eliminate nearly 30% of the antigen-antibody interaction in a dose-dependent manner, which was similar to the performance of the 31-mer peptide in SPR competitive inhibition assay. The competing Macrocarpal B bound to the immobilized PLA2R with an affinity of approximately 1.1Μm, whereas no interaction was detected between it and anti-PLA2R antibody/IgG.
Conclusion
We found a small molecular compound, Macrocarpal B, which could efficiently abrogate the binding between PLA2R and anti-PLA2R antibodies. These findings may have potential clinical value.