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New tetrapeptide ligands designed for antibody purification with biomimetic chromatography: Molecular simulation and experimental validation

Paper ID Volume ID Publish Year Pages File Format Full-Text
2689 126 2016 11 PDF Available
Title
New tetrapeptide ligands designed for antibody purification with biomimetic chromatography: Molecular simulation and experimental validation
Abstract

•A small, deliberately designed library of tetrapeptide ligands was established.•Accurate screening for the library was performed via molecular docking and molecular dynamics simulation.•The resin coupled with the novel tetrapeptide ligand, Ac-YFRH, showed high capacity in the wide operation range.•The novel resin showed satisfying purification performance for antibody.

Peptide ligands have been developed as powerful alternatives to Protein A for antibody purification. In this study, a tetrapeptide library with two aromatic residues, one arginine and one aromatic/aliphatic residue (Aro-Aro-R-Aro/Ali) was constructed considering molecular interactions and applications. The library had 128 peptide ligands and was screened by flexible docking and molecular dynamics simulation. The results indicated that Ac-YFRH was the best ligand, and then was coupled onto an aminated argarose matrix. The results of isotherm adsorption showed that the binding capacity of human immunoglobulin G (IgG) was high at pH 7–8 and low at pH 4–5. The IgG adsorption also showed obvious salt-independence, and the addition of salt could reduce unspecific adsorption caused by electrostatic interaction. After the optimization of pH and salt addition, high IgG purity of 98.4% could be obtained with the recovery of 89.4% from BSA-containing feedstock. The purification of monoclonal antibody from CHO cell culture supernatant was tested, and the purity and recovery reached 98.0% and 79.5%, respectively. The results demonstrated that the new resin with the tetrapeptide YFRH ligand had high affinity and flexible operation window for IgG purification.

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Keywords
Chromatography; Peptide ligands; Antibodies; Purification; Tetrapeptide; Molecular simulation
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New tetrapeptide ligands designed for antibody purification with biomimetic chromatography: Molecular simulation and experimental validation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 114, 15 October 2016, Pages 191–201
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us