Protein engineering enables the creation of tailor-made proteins for a variety of applications. ImmTACs stand out as promising therapeutics for cancer and other treatments while also presenting unique challenges for stability, formulation, and delivery. We have shown that ImmTACs behave as Janus particles in solution, leading to self-association at low concentrations, even when the average protein–protein interactions suggest that the molecule should be stable. The formation of small but stable oligomers was confirmed by static and dynamic light scattering and analytical ultracentrifugation. Modeling of the structure using AlphaFold leads to a rational explanation for this behavior, consistent with the Janus particle assembly observed for inverse patchy particles.

中文翻译：

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合成的 T 细胞受体样蛋白在溶液中表现为 Janus 颗粒


蛋白质工程能够为各种应用创建定制的蛋白质。ImmTAC 作为有前途的癌症和其他治疗疗法脱颖而出，同时也对稳定性、配方和递送提出了独特的挑战。我们已经证明，ImmTACs 在溶液中表现为 Janus 颗粒，导致在低浓度下自缔合，即使平均蛋白质-蛋白质相互作用表明分子应该是稳定的。通过静态和动态光散射以及分析超速离心证实了小而稳定的低聚物的形成。使用 AlphaFold 对结构进行建模可以合理地解释这种行为，这与观察到的逆斑块状粒子的 Janus 粒子组装一致。