APN-PEG4-Tetrazine is a heterobifunctional PEG linker combining an APN moiety with high cysteine selectivity and a tetrazine group for rapid inverse electron-demand Diels-Alder (iEDDA) reactions with strained alkenes like TCO, norbornene, and cyclopropene. Its stable APN–cysteine conjugates resist hydrolysis in aqueous media, human plasma, and living cells. Featuring a hydrophilic PEG4 spacer, it reduces steric hindrance, improves solubility, and enhances bioconjugation efficiency. Biocompatible and chemoselective, this linker enables fast, catalyst-free, copper-free click reactions for antibody-drug conjugates, fluorescent imaging, drug delivery, and other bioconjugation applications.
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