TY - JOUR
T1 - Orientation of monoclonal antibodies in ion-exchange chromatography
T2 - A predictive quantitative structure–activity relationship modeling approach
AU - Kittelmann, Jörg
AU - Lang, Katharina M H
AU - Ottens, Marcel
AU - Hubbuch, Jürgen
PY - 2017/8/11
Y1 - 2017/8/11
N2 - Chromatographic separation of biopharmaceuticals in general and monoclonal antibodies (mAbs) specifically is the bottleneck in terms of cost and throughput in preparative purification. Still, generalized platform processes are used, neglecting molecule specific characteristics, defining protein-resin interaction terms. Currently used in silico modeling approaches do not consider the orientation of the molecule towards the chromatographic resins as a result of the structural features on an atomic level. This paper describes a quantitative structure–activity relationship (QSAR) approach to model the orientation of mAbs on ion exchange chromatographic matrices as a function of property distribution and mobile phase characteristics. 6 mAbs were used to build a predictive QSAR model and to investigate the preferred binding orientations and resulting surface shielding on resins. Thereby different dominating orientations, caused by composition of Fab fragments of the mAbs, could be identified. The presented methodology is suitable to gain extended insight in molecule orientation on chromatographic resins and to tailor purification strategies based on molecule structure.
AB - Chromatographic separation of biopharmaceuticals in general and monoclonal antibodies (mAbs) specifically is the bottleneck in terms of cost and throughput in preparative purification. Still, generalized platform processes are used, neglecting molecule specific characteristics, defining protein-resin interaction terms. Currently used in silico modeling approaches do not consider the orientation of the molecule towards the chromatographic resins as a result of the structural features on an atomic level. This paper describes a quantitative structure–activity relationship (QSAR) approach to model the orientation of mAbs on ion exchange chromatographic matrices as a function of property distribution and mobile phase characteristics. 6 mAbs were used to build a predictive QSAR model and to investigate the preferred binding orientations and resulting surface shielding on resins. Thereby different dominating orientations, caused by composition of Fab fragments of the mAbs, could be identified. The presented methodology is suitable to gain extended insight in molecule orientation on chromatographic resins and to tailor purification strategies based on molecule structure.
KW - Binding orientation
KW - Ion-exchange chromatography
KW - Monoclonal antibody (mAb)
KW - Predictive modeling
KW - Quantitative structure–activity relationship (QSAR)
UR - http://www.scopus.com/inward/record.url?scp=85021219874&partnerID=8YFLogxK
U2 - 10.1016/j.chroma.2017.06.047
DO - 10.1016/j.chroma.2017.06.047
M3 - Article
C2 - 28655394
SN - 0021-9673
VL - 1510
SP - 33
EP - 39
JO - Journal of Chromatography A
JF - Journal of Chromatography A
ER -