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A Novel Type of PD-L1 Inhibitor rU1 snRNPA From Human-Derived Protein Scaffolds Library

Front Oncol.. 2021-11; 
Chuang Ma, Sennan Qiao, Zhiyi Liu, Liang Shan, Chongyang Liang, Meiling Fan, Fei Sun
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Recombinant Proteins Next, 3.0 μl of 1 mg/mL PD-1 (Genscript, Z03370) and 20μl of SERS reporter 4-ABP (5.0 mM) were mixed with the AgNPs solution (1.0 ml, 0.30nM) for 2 h at room temperature, and unreacted molecules were removed by centrifugation (4000g for 7 min).Nonspecific binding chemicals and antibodies were washed by centrifugation, and the remaining antibody-conjugated AgNPs were resuspended in the PBS buffer solution. Thus, the prepared AgNPs@PD-1@4-ABP was ready for use. Next, we conjugated PD-L1 (Genscript, Z03371) onto the surfaces of magnetic beads. Get A Quote

摘要

Three marketed anti-PD-L1 antibodies almost have severe immune-mediated side effects. The therapeutic effects of anti-PD-L1 chemical inhibitors are not satisfied in the clinical trials. Here we constructed human-derived protein scaffolds library and screened scaffolds with a shape complementary to the PD-1 binding domain of PD-L1. The RNA binding domain of U1 snRNPA was selected as one of potential binders because it had the most favorable binding energies with PD-L1 and conformed to pre-established biological criteria for the screening of candidates. The recombinant U1 snRNPA (rU1 snRNPA) in Escherichia coli exhibits anti-cancer activity in melanoma and breast cancer by reactivating tumor-suppressed T cells in... More

关键词

PD-L1; breast cancer; human-derived; inhibitor; melanoma; scaffold