Glycosylation influences on the aggregation propensity of therapeutic monoclonal antibodies.
Monoclonal antibodies are the fastest growing class of biologics in the pharmaceutical industry. The correlation between mAb glycosylation and aggregation has not been elucidated in detail, yet understanding the structure-stability relationship involving glycosylation is critical for developing successful drug formulations. We conducted studies of temperature-induced aggregation and compared the stability of both glycosylated and aglycosylated forms of a human IgG1. In parallel, we also performed molecular dynamics simulations of the glycosylated full antibody to gain an understanding of the polysaccharide surroundings at the molecular level. Aglycosylated mAbs are somewhat less stable and therefore aggregate more easily than the glycosylated form at the temperatures studied. Glycosylation seems to enhance solubility and stability of these therapeutics and thus might be important for long-term storage.
Department of Chemical Engineering, MIT, Cambridge, MA, USA.
Veysel
V
Kayser
Naresh
N
Chennamsetty
Vladimir
V
Voynov
Kurt
K
Forrer
Bernhard
B
Helk
Bernhardt L
BL
Trout
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D055550:Protein Stability; D013696:Temperature
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G