Song Ziyuan, Zheng Nan, Ba Xiaochu, Yin Lichen, Zhang Rujing, Ma Liang, Cheng Jianjun
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign , 1304 West Green Street, Urbana, Illinois 61801, United States.
Biomacromolecules. 2014 Apr 14;15(4):1491-7. doi: 10.1021/bm5001026. Epub 2014 Mar 17.
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.
通过氯官能化氨基酸N-羧基环酐单体的可控开环聚合，随后与三乙膦进行一步亲核取代反应，合成了带有季鏻侧链的多肽。所得多肽的构象可通过调节侧链长度和α-碳立体化学来控制。具有11个σ键主链到电荷距离的基于鏻的聚（L-谷氨酸）衍生物在pH和离子强度变化时采用稳定的α-螺旋构象。这些螺旋状、带有季鏻的多肽比它们的外消旋和无规卷曲类似物表现出更高的细胞穿透能力。它们主要通过能量非依赖、非内吞的细胞膜转导机制进入细胞，并表现出低细胞毒性，证实了它们作为安全有效的细胞穿透剂的潜在用途。
