title: 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 α-carbon stereochemistry. The phosphonium-based poly(l-glutamate) derivatives with 11 σ-bond backbone-to-charge distance adopt stable α-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.
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, Illinois 61801, United States.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Song
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Ba
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.forename: Rujing
authors.initials: R
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D002462:Cell Membrane / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010757:Phosphorous Acids / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D010757:Phosphorous Acids; D011099:Polyglutamic Acid