Small-Angle Neutron Scattering Characterization of Monoclonal Antibody Conformations and Interactions at High Concentrations

Published

August 6, 2013

Author(s)

Eric J. Yearley, Isidro E. Zarraga, Steven J. Shire, Thomas M. Scherer, Yatin Gokarn, Norman J. Wagner, Yun Liu

Abstract

Small-angle neutron scattering (SANS) has been used to probe the solution structure of two protein therapeutics (MAb2 and MAb2) and their inter-protein potentials at high concentrations. These MAbs differ by small primary sequence variations in the complementarity determining region, but show very large differences in solution viscosity. The analysis of SANS patterns as a function of different solution conditions suggests that intra-molecular structural features of MAb1 and MAb2 are not significantly altered despite the various concentrations and experimental conditions used. However, with increasing concentration, the average PPI gradually becomes dominated by a repulsive interaction potential. Conversely, MAb2 displays a highly repulsive interaction potential throughout the entire concentration series probed. Even though the substantially higher MAb1 solution viscosity correlates very well with the large scale structure induced by the attractive potential, ther is no such strong correlation when varying the pH and slat conditions of MAb1 samples.

Citation

Biophysical Journal

Volume

105

Pub Type

Journals

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Keywords

small angle neutron scattering, moncclonal antibody, protein interaction, viscosity

Citation

Yearley, E. , Zarraga, I. , Shire, S. , Scherer, T. , Gokarn, Y. , Wagner, N. and Liu, Y. (2013), Small-Angle Neutron Scattering Characterization of Monoclonal Antibody Conformations and Interactions at High Concentrations, Biophysical Journal, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=912835 (Accessed July 18, 2024)