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.

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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
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article

AbClick Pro H: Scavenger-Free, Traceless Lys248 Conjugation Via O -Acyl Hydroxamate Chemistry for Homogeneous Antibody–Drug Conjugates (ADCs)

Sang Jeon Chung, Y. Lee, Nayoung Ko, S Park et al.
Organic Letters
HER2/EGFR in Cancer Research
article

AbClick Pro H: Scavenger-Free, Traceless Lys248 Conjugation Via O -Acyl Hydroxamate Chemistry for Homogeneous Antibody–Drug Conjugates (ADCs)

Sang Jeon Chung, Y. Lee, Nayoung Ko, S Park, Ju Hwan Kim, JunSeok Son, J. W. Seo, Taedong Han, Hojin Yeom, Jinyoung Kim
article en

Abstract

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.

Organic LettersVol. 28(2)
Green Cross (United States) (US), Bio-Medical Science (South Korea) (KR), Sungkyunkwan University (KR)
Industry, innovation and infrastructure
Openalex Percentile: Top 29%
HER2/EGFR in Cancer Research
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