B9 protein binder

B9 protein binder is a de novo designed protein binder developed by researchers at ShanghaiTech University, Shanghai Jiao Tong University, the Shanghai Institute of Organic Chemistry (Chinese Academy of Sciences), and Fudan University. It was designed using AI-driven protein design tools, including RFdiffusion and ProteinMPNN, to target and stabilize the conserved region (CR-helix) within the low-complexity domain (LCD) of transactive response DNA binding protein of 43 kDa (TDP-43). By binding to the CR-helix with nanomolar affinity (approximately 87.9 nM), B9 prevents the conformational transition of TDP-43 from an alpha-helix to a beta-strand, thereby inhibiting its pathological amyloid aggregation. In preclinical models, B9 has demonstrated the ability to significantly reduce TDP-43 aggregation and lower phosphorylated TDP-43 (pTDP-43 S409/410) levels in both nuclear and cytoplasmic cellular models, representing a promising therapeutic candidate for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD).

Other names

B9B-9B 9B9 TDP-43 binderB-9 TDP-43 binderB 9 TDP-43 binderB9 proteinB-9 proteinB 9 protein