Laber Joshua R, Laue Thomas M, Filoti Dana I
Formulation and Biologics Product Development, Nektar Therapeutics, 455 Mission Bay Boulevard South, San Francisco, CA 94158, USA.
Carpenter Professor Emeritus, University of New Hampshire, Durham, NH 03824, USA.
Antib Ther. 2022 Jul 28;5(3):211-215. doi: 10.1093/abt/tbac018. eCollection 2022 Jul.
The diffusion interaction parameter ( ) has been demonstrated to be a high-throughput technique for characterizing interactions between proteins in solution. reflects both attractive and repulsive interactions, including long-ranged electrostatic repulsions. Here, we plot the mutual diffusion coefficient ( ) as a function of the experimentally determined Debye-Hückel-Henry surface charge ( ) for seven human monoclonal antibodies (mAbs) in 15 mM histidine at pH 6. We find that graphs of versus intersect at ~ 2.6, independent of protein concentration. The same data plotted as versus show a transition from net attractive to net repulsive interactions in the same region of the intersection point. These data suggest that there is a minimum surface charge necessary on these mAbs needed to overcome attractive interactions.
扩散相互作用参数（ ）已被证明是一种用于表征溶液中蛋白质间相互作用的高通量技术。 反映了吸引和排斥相互作用，包括长程静电排斥。在此，我们绘制了7种人源单克隆抗体（mAb）在pH 6的15 mM组氨酸溶液中，互扩散系数（ ）随实验测定的德拜 - 休克尔 - 亨利表面电荷（ ）的变化曲线。我们发现， 与 的曲线在 约为2.6处相交，与蛋白质浓度无关。以 与 绘制的相同数据显示，在 交点的相同区域内，相互作用从净吸引转变为净排斥。这些数据表明，这些单克隆抗体需要有一个最小表面电荷来克服吸引相互作用。
