ArticlePharmaceutical research2014
Assessment of physical stability of an antibody drug conjugate by higher order structure analysis: impact of thiol- maleimide chemistry.
Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 66 citations in OpenAlex.
- Antibody-Drug Conjugates Drug Product Formulation and Process Development, Scalability and Stability Considerations.AAPS PharmSciTech · 2026Review
- Formulation Matters: The Overlooked Engine of Stability and Success in Antibody-Drug Conjugates.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Structural Fingerprint of Therapeutic Monoclonal Antibodies Determined Using a Combination of Near-UV Circular Dichroism and Statistical Approach for Comparative Analysis.Analytical chemistry · 2025Article
- Antibody-Drug Conjugates (ADCs): current and future biopharmaceuticals.Journal of hematology & oncology · 2025Review
- Fundamental properties and principal areas of focus in antibody-drug conjugates formulation development.Antibody therapeutics · 2025Review
- A Novel Size Exclusion Chromatography Method for the Analysis of Monoclonal Antibodies and Antibody-drug Conjugates by Using Sodium Iodide in the Mobile Phase.Pharmaceutical research · 2024Article
- Cetuximab-based PROteolysis targeting chimera for effectual downregulation of NSCLC with varied EGFR mutations.International journal of biological macromolecules · 2023Article
- Analyzing protein conjugation reactions for antibody-drug conjugate synthesis using polarized excitation emission matrix spectroscopy.Biotechnology and bioengineering · 2022Article
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- Site-specific glycan-conjugated NISTmAb antibody drug conjugate mimetics: synthesis, characterization, and utility.Analytical and bioanalytical chemistry · 2021Article
- Development and preclinical evaluation of cixutumumab drug conjugates in a model of insulin growth factor receptor I (IGF-1R) positive cancer.Scientific reports · 2020Article
- Evaluation of hydrophobic-interaction chromatography resins for purification of antibody-drug conjugates using a mimetic model with adjustable hydrophobicity.Journal of separation science · 2020Article
- Antibody Conjugates-Recent Advances and Future Innovations.Antibodies (Basel, Switzerland) · 2020Review
- The Properties of Cysteine-Conjugated Antibody-Drug Conjugates Are Impacted by the IgG Subclass.The AAPS journal · 2018Article
- Conformational Assessment of Adnectin and Adnectin-Drug Conjugate by Hydrogen/Deuterium Exchange Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2018Article
- In-Depth Comparison of Lysine-Based Antibody-Drug Conjugates Prepared on Solid Support Versus in Solution.Antibodies (Basel, Switzerland) · 2018Article
- In-silico prediction of concentration-dependent viscosity curves for monoclonal antibody solutions.mAbs · 2017Article
- Antibody Aggregation: Insights from Sequence and Structure.Antibodies (Basel, Switzerland) · 2016Review
- Current ADC Linker Chemistry.Pharmaceutical research · 2015Review
- Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability.Pharmaceutical research · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo provide a systematic biophysical approach towards a better understanding of impact of conjugation chemistry on higher order structure and physical stability of an antibody drug conjugate (ADC).
methodsADC was prepared using thiol-maleimide chemistry. Physical stabilities of ADC and its parent IgG1 mAb were compared using calorimetric, spectroscopic and molecular modeling techniques.
resultsADC and mAb respond differently to thermal stress. Both the melting temperatures and heat capacities are substantially lower for the ADC. Spectroscopic experiments show that ADC and mAb have similar secondary and tertiary structures, but these are more easily destabilized by thermal stress on the ADC indicating reduced conformational stability. Molecular modeling calculations suggest a substantial decrease in the conformational energy of the mAb upon conjugation. The local surface around the conjugation sites also becomes more hydrophobic in the ADC, explaining the lower colloidal stability and greater tendency of the ADC to aggregate.
conclusionsComputational and biophysical analyses of an ADC and its parent mAb have provided insights into impact of conjugation on physical stability and pinpointed reasons behind lower structural stability and increased aggregation propensity of the ADC. This knowledge can be used to design appropriate formulations to stabilize the ADC.
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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.