Balancing Reactivity and Specificity: Fc-Binding <i>O</i>-Acyl Hydroxamate Reagents for Site-Selective Antibody Labeling at Lys248
We report the design and synthesis of <i>O</i>-acyl hydroxamates (OAHs) affinity labels for selective modification of human IgG1 at Lys248 via proximity-driven acylation. Optimized compound <b>7g</b> exhibits high water stability and >99% site-selective conversion at Lys248 on Trastuzumab using only 3 equiv. Peptide mapping and fluorescence labeling confirm its precision, establishing <b>7g</b> as a robust platform for efficient and site-selective antibody conjugation.
Authors
- Sang Jeon Chung (ORCID: https://orcid.org/0000-0002-3501-212X)
- Sun Hee Park (ORCID: https://orcid.org/0000-0001-5648-9237)
- Seong‐Hyun Park (ORCID: https://orcid.org/0000-0002-0982-5338)
- Taedong Han
- Jinyoung Kim (ORCID: https://orcid.org/0000-0002-5862-0363)
- Jin-Woo Seo (ORCID: https://orcid.org/0000-0002-1624-745X)
- Tae‐Jin Lee (ORCID: https://orcid.org/0000-0001-6091-542X)
- Ju Hwan Kim
Institutions
- Bio-Medical Science (South Korea) (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1021/acs.orglett.5c01424
- Citations
- 3
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 4.08
Funders
- National Research Foundation of Korea