Self-Interactions of Two Monoclonal Antibodies: Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling

被引：8

作者：

Mahapatra, Sujata ^{[1
,2
,3
]}

Polimeni, Marco ^{[4
]}

Gentiluomo, Lorenzo ^{[5
,6
,7
]}

Roessner, Dierk ^{[5
]}

Friess, Wolfgang ^{[6
]}

Peters, Guenther H. J. ^{[2
]}

Streicher, Werner W. ^{[1
,8
]}

Lund, Mikael ^{[4
,9
]}

Harris, Pernille ^{[2
,10
]}

机构：

[1] Novozymes AS, DK-2800 Lyngby, Denmark

[2] Tech Univ Denmark, Dept Chem, DK-2800 Lyngby, Denmark

[3] Dept Mol Biol & Genet, Gustav Wieds Vej 10,Bldg 3135,1-14, DK-8000 Aarhus C, Denmark

[4] Lund Univ, Dept Chem, Div Theoret Chem, S-22362 Lund, Sweden

[5] Wyatt Technol Europe GmbH, D-56307 Dernbach, Germany

[6] Ludwig Maximilians Univ Munchen, Dept Pharm Pharmaceut Technol & Biopharmaceut, D-81377 Munich, Germany

[7] Coriolis Pharma, Fraunhoferstr 18B, D-82152 Munich, Germany

[8] NanoTemper Technol GmbH, Floessergasse 4, D-81369 Munich, Germany

[9] Lund Univ, Adv Xray & Neutron Sci LINXS, S-22370 Lund, Sweden

[10] Univ Copenhagen, Dept Chem, Univ Pk 5, DK-2100 Copenhagen, Denmark

来源：

MOLECULAR PHARMACEUTICS | 2022年 / 19卷 / 02期

基金：

欧盟地平线“2020”;

关键词：

monoclonal antibodies; light scattering; small-angle X-ray scattering; Monte Carlo simulations; course-grained modeling; osmotic second virial coefficient; structure factor; colloidal stability; protein aggregation; PROTEIN-PROTEIN INTERACTIONS; IONIC-STRENGTH; FORMULATION; ELECTROSTATICS; AGGREGATION; ASSOCIATION; SIMULATION; SUITE;

D O I：

10.1021/acs.molpharmaceut.1c00627

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Using light scattering (LS), small-angle X- ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B-22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a twoprotein model to predict B-22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.

引用

页码：508 / 519

页数：12

共 57 条

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