VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • A deep dive into spin-labeled polysorbate’s interaction with therapeutic antibody using 2D NMR, EPR and MD simulations [Elektronski vir]
    Lebar, Blaž ...
    Polysorbates (PS) are widely used surfactants in biopharmaceutical formulations playing a crucial role in protecting proteins against mechanical stress and interface-induced damage. However, their ... susceptibility to degradation can compromise their function and lead to particle formation. Recent studies suggest that monoclonal antibodies (mAbs) may mitigate PS degradation catalyzed by histidine chloride buffer, indicating the presence of protein-PS interactions. In this study, we investigated these interactions using NMR, starting with 1H T2 CPMG filter experiments and methyl fingerprinting, which failed to detect interactions. To enhance sensitivity, we synthesized spin-labeled PS (SLPS), enabling paramagnetic relaxation enhancement (PRE) NMR experiments, specifically amide fingerprinting, which successfully revealed interactions. Complementary electron paramagnetic resonance (EPR) measurements of SLPS and mAb also detected interactions, but only in the presence of sucrose, underscoring their weak and transient nature. Additionally, molecular dynamics simulations identified potential interaction hotspots on the antibody structure, providing mechanistic insights into these interactions.
    Vrsta gradiva - e-članek ; neleposlovje za odrasle
    Leto - 2025
    Jezik - angleški
    COBISS.SI-ID - 255171075