ArticlemAbs2015
Rational design of viscosity reducing mutants of a monoclonal antibody: hydrophobic versus electrostatic inter-molecular interactions.
Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed.
- Article
- Article
- Fab-Fc and Fab-Fab interactions of variable strength and valency contribute to the high concentration viscosity of IgGProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Polysorbates' effects on molecular and thermodynamic properties of phosphorodiamidate morpholino oligonucleotides' structures.Molecular therapy. Nucleic acids · 2026Article
- Review
- Article
- Article
- Article
- Large language models for drug discovery and development.Patterns (New York, N.Y.) · 2025Review
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Prediction of aggregation in monoclonal antibodies from molecular surface curvature.Scientific reports · 2025Article
- Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data.Communications biology · 2025Article
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- A Practical Guide to Computational Tools for Engineering Biocatalytic Properties.International journal of molecular sciences · 2025Review
- Antigen-presenting cell internalization is key for understanding and evaluating therapeutic antibodies' immunogenicity.Frontiers in immunology · 2025Review
- A framework for the biophysical screening of antibody mutations targeting solvent-accessible hydrophobic and electrostatic patches for enhanced viscosity profiles.Computational and structural biotechnology journal · 2024Article
- A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.ACS pharmacology & translational science · 2024Article
- The Relationship between Protein-Protein Interactions and Liquid-Liquid Phase Separation for Monoclonal Antibodies.Molecular pharmaceutics · 2023Article
- Low-data interpretable deep learning prediction of antibody viscosity using a biophysically meaningful representation.Scientific reports · 2023Article
- Structure-Based Optimization of Antibody-Based Biotherapeutics for Improved Developability: A Practical Guide for Molecular Modelers.Methods in molecular biology (Clifton, N.J.) · 2023Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region. The disruption of an APR that lies at the interface of light and heavy chain variable domains, VH and VL, via L45K mutation destabilized MAB 1 and abolished antigen binding. However, mutation at the preceding residue (V44K), which also lies in the same APR, increased apparent solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or thermal stability. Neutralizing the negatively charged surface patch (E59Y) also increased apparent solubility and reduced viscosity of MAB 1, but charge reversal at the same position (E59K/R) caused destabilization, decreased solubility and led to difficulties in sample manipulation that precluded their viscosity measurements at high concentrations. Both V44K and E59Y mutations showed similar increase in apparent solubility. However, the viscosity profile of E59Y was considerably better than that of the V44K, providing evidence that inter-molecular interactions in MAB 1 are electrostatically driven. In conclusion, neutralizing negatively charged surface patches may be more beneficial toward reducing viscosity of highly concentrated antibody solutions than charge reversal or aggregation prone motif disruption.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.