Parallel screening of selective and high-affinity displacers for proteins in ion-exchange systems.
This paper employs a parallel batch screening technique for the identification of both selective and high-affinity displacers for a model binary mixture of proteins in a cation-exchange system. A variety of molecules were screened as possible displacers for the proteins ribonuclease A (RNAseA) and alpha-chymotrypsinogen A (alpha-chyA) on high performance Sepharose SP. The batch screening data for each protein was used to select leads for selective and high-affinity displacers and column experiments were carried out to evaluate the performance of the selected leads. The data from the batch displacements was also employed to generate quantitative structure-efficacy relationship (QSER) models based on a support vector machine regression approach. The resulting models had high correlation coefficients and were able to predict the behaviour of molecules not included in the training set. The descriptors selected in the QSER models for both proteins were examined to provide insights into factors influencing displacer selectivity in ion-exchange systems. The results presented in this paper demonstrate that this parallel batch screening-QSER approach can be employed for the identification of selective and high-affinity displacers for protein mixtures.
Rege
Kaushal
K
Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA.
Ladiwala
Asif
A
Tugcu
Nihal
N
Breneman
Curt M
CM
Cramer
Steven M
SM
D002411:Cation Exchange Resins; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002852:Chromatography, Ion Exchange / Q000379:methods*; D011506:Proteins / Q000302:isolation & purification*
D002411:Cation Exchange Resins; D011506:Proteins