MFS03

The MFS03 (maleimido fluorosulfonyl) linker is a heterobifunctional covalent tether that converts affinity proteins (affibody and monobody) into irreversible therapeutics. MFS03 features a maleimide for cysteine conjugation and a bio-orthogonal aryl fluorosulfate warhead on a flexible spacer (2.92–17.7 Å), which initiates a proximity-enabled Sulfur(VI) Fluoride Exchange (SuFEx) reaction with target nucleophiles like histidine or lysine. On HER2/EGFR scaffolds, this covalent anchoring enhances therapeutic performance, yielding >2-fold tumor retention, 185% higher cellular uptake, and near-complete tumor inhibition. This permanent binding decouples pharmacodynamics from pharmacokinetics, boosting cytotoxicity 2.5- to 4.9-fold (to 0.31 nM) while maintaining a favorable biosafety profile.