Abstract
A traceless O-acyl hydroxamate Fc-binding peptide linker enables rapid, scavenger-free, and site-selective conjugation at Lys248 of human IgG1. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 764-767 |
| Number of pages | 4 |
| Journal | Organic Letters |
| Volume | 28 |
| Issue number | 2 |
| DOIs | |
| State | Published - 16 Jan 2026 |
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