Biomimetic N ‐cyano sulfoximine–thiazole ligation for antibody–drug conjugate assembly
Abstract We report the first application of N ‐cyano sulfoximine‐mediated thiazole ligation to antibody–drug conjugate (ADC) assembly. A bifunctional N ‐cyano sulfoximine–maleimide linker bearing a pyrimidine core was synthesized and installed on trastuzumab via thiol–maleimide chemistry, as confirmed by ESI‐QTOF analysis of all eight interchain cysteine sites. Subsequent ligation with an N ‐terminal cysteine‐functionalized rhodamine (Cys–rhodamine) model payload under mild aqueous conditions (PBS, pH 7.4) afforded model ADCs with tunable drug‐to‐antibody ratios (DAR). Stepwise payload addition (25 equiv., 2 h intervals) achieved DAR 8 within 10–12 h, corresponding to full occupancy of all conjugation sites. These findings establish biomimetic thiazole ligation as a viable platform for chemo‐selective ADC construction.
Authors
- H.J. Lim (ORCID: https://orcid.org/0000-0002-7724-1094)
- Do Hyun Kang (ORCID: https://orcid.org/0000-0001-6588-0000)
- Seong Jun Park (ORCID: https://orcid.org/0000-0003-1767-0900)
- Ji Young Hyun (ORCID: https://orcid.org/0000-0002-5029-2676)
- Ju Yeon Lee (ORCID: https://orcid.org/0000-0003-0855-6516)
- Eunsil Kim
- Ji Ho Song
- Na Ryeong Kim
Institutions
- Biocon (Switzerland) (CH)
- Korea Institute of Machinery & Materials (KR)
- Korea Basic Science Institute (KR)
- Korea Research Institute of Chemical Technology (KR)
- Chung-Ang University (KR)
- Korea University of Science and Technology (KR)
Publication Details
- Journal
- Bulletin of the Korean Chemical Society
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1002/bkcs.70233
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Trade, Industry and Energy
- Korea Research Institute of Chemical Technology
- Korea Drug Development Fund
- National Research Council of Science and Technology
- Ministry of Science and ICT, South Korea