Polypeptides with Quaternary Phosphonium Side Chains: Synthesis, Characterization, and Cell-Penetrating Properties

Ziyuan Song, Nan Zheng, Xiaochu Ba, Lichen Yin, Rujing Zhang, Liang Ma, Jianjun Cheng

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Abstract

Polypeptides bearing quaternary phosphonium side chains were synthesized via controlled ring-opening polymerization of chlorine-functionalized amino acid N-carboxyanhydride monomers followed by one-step nucleophilic substitution reaction with triethylphosphine. The conformation of the resulting polypeptides can be controlled by modulating the side-chain length and alpha-carbon stereochemistry. The phosphonium-based poly(L-glutamate) derivatives with 11 sigma-bond backbone-to-charge distance adopt stable alpha-helical conformation against pH and ionic strength changes. These helical, quaternary phosphonium-bearing polypeptides exhibit higher cell-penetrating capability than their racemic and random-coiled analogues. They enter cells mainly via an energy-independent, nonendocytic cell membrane transduction mechanism and exhibit low cytotoxicity, substantiating their potential use as a safe and effective cell-penetrating agent.
Original languageEnglish
JournalBiomacromolecules
Volume15
Issue number4
Pages (from-to)1491-1497
Number of pages7
ISSN1525-7797
DOIs
Publication statusPublished - 2014
Externally publishedYes

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