Work

Use of Debye–Hückel–Henry charge measurements in early antibody development elucidates effects of non-specific association

Year: 2022

Type: article

Abstract: The diffusion interaction parameter (kD) has been demonstrated to be a high-throughput technique for characterizing interactions between proteins in solution. kD reflects both attractive and repulsive interactions, including long-ranged electrostatic repulsions. Here, we plot the mutual diffusion coefficient (Dm) as a function of the experimentally determined Debye–Hückel–Henry surface charge (ZDHH) for seven human monoclonal antibodies (mAbs) in 15 mM histidine at pH 6. We find that graphs of Dm versus ZDHH intersect at ZDHH, ~ 2.6, independent of protein concentration. The same data plotted as kD versus ZDHH show a transition from net attractive to net repulsive interactions in the same region of the ZDHH intersection point. These data suggest that there is a minimum surface charge necessary on these mAbs needed to overcome attractive interactions.

Source: Antibody Therapeutics

DOI: 10.1093/abt/tbac018

Authors: Joshua R Laber, Thomas M Laue, Dana I Filoti

Institutions: Nektar Therapeutics (United States), University of New Hampshire, AbbVie (United States)

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,625

Funder: AbbVie