תקציר
The SARS-COV-2 virus is a deadly agent of inflammatory respiratory disease.
Since 2020, studies have focused on developing new therapies based on galactose-rich IgA
antibodies. Clinical surveys have also revealed that galactose-deficient IgA1 polymerizes in
serum, producing IgA nephropathy, which is a common cause of kidney failure in young adults.
Here we show that IgA1−IgA2 dimers are efficiently and economically purified in solution via
conjugated nonionic surfactant micellar aggregates. Quantitative capture at pH 7 and extraction
at pH 6.5 can avoid antibody exposure to acidic, potentially denaturing conditions. Brij-O20
aggregates lead to the highest process yields (88−91%) and purity (94%). Recovered IgA
dimers preserve their native secondary structure and do not self-associate. Increasing the
reaction volume has little impact on yield or purity. By introducing an efficient, inexpensive IgA
purification protocol, we assist pharmaceutical firms and research laboratories in developing
new IgA-based therapies as well as in increasing our understanding of IgA1 polymerization.
Since 2020, studies have focused on developing new therapies based on galactose-rich IgA
antibodies. Clinical surveys have also revealed that galactose-deficient IgA1 polymerizes in
serum, producing IgA nephropathy, which is a common cause of kidney failure in young adults.
Here we show that IgA1−IgA2 dimers are efficiently and economically purified in solution via
conjugated nonionic surfactant micellar aggregates. Quantitative capture at pH 7 and extraction
at pH 6.5 can avoid antibody exposure to acidic, potentially denaturing conditions. Brij-O20
aggregates lead to the highest process yields (88−91%) and purity (94%). Recovered IgA
dimers preserve their native secondary structure and do not self-associate. Increasing the
reaction volume has little impact on yield or purity. By introducing an efficient, inexpensive IgA
purification protocol, we assist pharmaceutical firms and research laboratories in developing
new IgA-based therapies as well as in increasing our understanding of IgA1 polymerization.
שפה מקורית | אנגלית אמריקאית |
---|---|
מספר המאמר | https://doi.org/10.1021/acsmedchemlett.4c00128 |
עמודים (מ-עד) | 979-986 |
מספר עמודים | 8 |
כתב עת | ACS Medicinal Chemistry Letters |
כרך | 15 |
מספר גיליון | 6 |
סטטוס פרסום | פורסם - 15 מאי 2024 |