ArticleScientific reports2023
Specific peptide conjugation to a therapeutic antibody leads to enhanced therapeutic potency and thermal stability by reduced Fc dynamics.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Evaluating the Efficacy of Monoclonal Antibodies Against a Bioactive Peptide Involved in Alzheimer's Disease: A Methodological Approach.Methods and protocols · 2026Article
- Enhancing Peptide Hydrophilicity of SPPS-Derived Peptides Using Fmoc Noncanonical Amino Acids: A Review.ACS biomaterials science & engineering · 2026Review
- Review
- Development of tCAP(N3): Affinity Peptide-Aided, pH-Triggered Strategy for Site-Specific Native IgG Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Cell-Penetrating Peptide-Based Triple Nanocomplex Enables Efficient Nuclear Gene Delivery in Chlamydomonas reinhardtii.Biotechnology and bioengineering · 2025Article
- A review of conjugation technologies for antibody drug conjugates.Antibody therapeutics · 2025Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibody-drug conjugates are powerful tools for combatting a wide array of cancers. Drug conjugation to a therapeutic antibody often alters molecular characteristics, such as hydrophobicity and effector function, resulting in quality deterioration. To develop a drug conjugation methodology that maintains the molecular characteristics of the antibody, we engineered a specific peptide for conjugation to the Fc region. We used trastuzumab and the chelator (DOTA) as model antibody and payload, respectively. Interestingly, peptide/DOTA-conjugated trastuzumab exhibited enhanced antibody-dependent cellular cytotoxicity (ADCC) and increased thermal stability. Detailed structural and thermodynamic analysis clarified that the conjugated peptide blocks the Fc dynamics like a "wedge." We revealed that (1) decreased molecular entropy results in enhanced ADCC, and (2) blockade of Fc denaturation results in increased thermal stability. Thus, we believe that our methodology is superior not only for drug conjugation but also as for reinforcing therapeutic antibodies to enhance ADCC and thermal stability.
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