Polypeptides with quaternary phosphonium side chains: synthesis, characterization, and cell-penetrating properties.

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 ?-carbon stereochemistry. The phosphonium-based poly(l-glutamate) derivatives with 11 ?-bond backbone-to-charge distance adopt stable ?-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.

SUBMITTER: Song Z 

PROVIDER: S-EPMC3993874 | biostudies-other | 2014 Apr

REPOSITORIES: biostudies-other