title: Interaction of arginine with Capto MMC in multimodal chromatography.
abstract: This study highlights the ability of arginine to elute bovine serum albumin (BSA) and a monoclonal antibody against interleukin-8 (mAb-IL8) from Capto MMC, which is a multimodal cation exchanger. Arginine provides high recovery of monomeric BSA from Capto MMC chromatography columns at yields similar to NaCl elution, and oligomeric BSA was more readily eluted by arginine than by NaCl. The effectiveness of arginine as an eluent also enabled the separation of monomeric BSA from the oligomeric forms. The purification of mAb-IL8 was successfully achieved using Capto MMC chromatography and arginine as the eluent. The mechanism of the effects of arginine on protein elution was determined by calculating the binding free energy between arginine and Capto MMC using molecular dynamics simulations. The overall affinity of arginine for Capto MMC was associated with electrostatic interactions. However, additional affinities contributed by hydrophobic interaction or hydrogen bonding were also observed to play a role in the interaction between arginine and Capto MMC, which likely results in the characteristic elution by arginine.
authors.affiliation: Nanosystem Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Alliance Protein Laboratories, San Diego, CA 92121, USA.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Koto, Tokyo 135-0064, Japan. Electronic address: kameda-tomoshi@aist.go.jp.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Kameda
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D001120:Arginine / Q000737:chemistry*; D002417:Cattle; D002845:Chromatography / Q000379:methods*; D016209:Interleukin-8 / Q000276:immunology; D056004:Molecular Dynamics Simulation; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D012710:Serum Albumin, Bovine; D001120:Arginine
keywords: Arginine; Free energy; Molecular dynamics simulation; Multimodal chromatography; Polyacrylamide gel electrophoresis