Modular solid-phase synthesis of electrophilic cysteine-selective ethynyl-phosphonamidate peptides.

ABSTRACT

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.