Assessment of the Protein-Protein Interactions in a Highly Concentrated Antibody Solution by Using Raman Spectroscopy

作者：Ota Chikashi^*; Noguchi Shintaro; Nagatoishi Satoru; Tsumoto Kouhei

来源：Pharmaceutical Research, 2016, 33(4): 956-969.

DOI：10.1007/s11095-015-1842-8

• antibody drug
• biopharmaceutical
• protein protein interaction
• Raman spectroscopy

To investigate the protein-protein interactions of a highly concentrated antibody solution that could cause oligomerization or aggregation and to develop a better understanding of the optimization of drug formulations.
In this study, we used Raman spectroscopy to investigate the structure and interactions of a highly concentrated antibody solution over a wide range of concentrations (10-200 mg/mL) with the aid of a multivariate analysis.
Our analysis of the amide I band, I (856) /I (830) of Tyr, and the relative intensity at 1004 cm(-1) of the Phe and OH stretching region at around 3000 cm(-1) showed that across this wide range of concentrations, the secondary structure of the IgG molecules did not change; however, short-range attractive interactions around the Tyr and Phe residues occurred as the distance between the IgG molecules decreased with increasing concentration. Analysis of the OH stretching region at around 3000 cm(-1) showed that these short-range attractive interactions correlated with the amount of hydrated water around the IgG molecules.
Our data show that Raman spectroscopy can provide valuable information of the protein-protein interactions based on conformational approaches to support conventional colloidal approaches, especially for analyses of highly concentrated solutions.

• 出版日期2016-4
• 单位河北医科大学