AbClick Pro H: Scavenger-Free, Traceless Lys248 Conjugation Via <i>O</i> -Acyl Hydroxamate Chemistry for Homogeneous Antibody–Drug Conjugates (ADCs)
A traceless <i>O</i>-acyl hydroxamate Fc-binding peptide linker enables rapid, scavenger-free, and site-selective conjugation at Lys248 of human IgG<sub>1</sub>. The resulting homogeneous DAR2 antibody-drug conjugates (ADCs) retain antigen binding and internalization with payload-dependent stability and cytotoxicity. The linker's intrinsic leaving-group mechanism ensures clean FcBP release and broad payload compatibility. This robust, scalable traceless Lys248 conjugation chemistry underpins investigational new drug (IND)-approved and nonclinical ADC pipelines, offering a predictable platform for next-generation ADC design.
Authors
- Sang Jeon Chung (ORCID: https://orcid.org/0000-0002-3501-212X)
- Y. Lee
- Nayoung Ko
- S Park
- Ju Hwan Kim
- JunSeok Son (ORCID: https://orcid.org/0000-0001-8344-4536)
- J. W. Seo
- Taedong Han
- Hojin Yeom
- Jinyoung Kim
Institutions
- Green Cross (United States) (US)
- Bio-Medical Science (South Korea) (KR)
- Sungkyunkwan University (KR)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-12-31
- DOI
- https://doi.org/10.1021/acs.orglett.5c04902
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00