Remediating agitation-induced antibody aggregation by eradicating exposed hydrophobic motifs
| Autor: | Kathy Manchulenko, Michael Brown, Cyr Clovis Chua De Imus, Ramil F. Latypov, Clark Rutilio H, Jane Carter, Zien Wilson, Randal R. Ketchem |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular engineering In silico Amino Acid Motifs Immunology Antibody Affinity Computational biology Protein aggregation thermal Interferon-gamma Protein Aggregates antibody Humans Immunology and Allergy Native structure Cells Cultured computational biology Protein Stability Chemistry aggregation Antibodies Monoclonal Computational Biology A protein modeling stability Molecular biology Protein Structure Tertiary Killer Cells Natural HEK293 Cells agitation in silico Immunoglobulin G Spatial aggregation biology.protein Drug product Stress Mechanical Protein Multimerization Antibody Hydrophobic and Hydrophilic Interactions Algorithms Reports Protein Binding |
| Zdroj: | mAbs |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | Therapeutic antibodies must encompass drug product suitable attributes to be commercially marketed. An undesirable antibody characteristic is the propensity to aggregate. Although there are computational algorithms that predict the propensity of a protein to aggregate from sequence information alone, few consider the relevance of the native structure. The Spatial Aggregation Propensity (SAP) algorithm developed by Chennamsetty et. al. incorporates structural and sequence information to identify motifs that contribute to protein aggregation. We have utilized the algorithm to design variants of a highly aggregation prone IgG2. All variants were tested in a variety of high-throughput, small-scale assays to assess the utility of the method described herein. Many variants exhibited improved aggregation stability whether induced by agitation or thermal stress while still retaining bioactivity. |
| Databáze: | OpenAIRE |
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