We report an efficient method to install electrophilic cysteine-selective ethynyl-phosphonamidates on peptides during Fmoc-based solid phase peptide synthesis (SPPS). By performing Staudinger-phosphonite reactions between different solid supported azido-peptides and varying ethynylphosphonites, we obtained ethynyl-phosphonamidate containing peptidic compounds after acidic deprotection, including an electrophilic cell-penetrating peptide that showed high efficiency as an additive for cellular delivery of proteins.
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