Efficient Delivery of Cyclic Peptides into Mammalian Cells with Short Sequence Motifs

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• 作者：Ziqing Qian ; Tao Liu ; Yu-Yu Liu ; Roger Briesewitz ; Amy M. Barrios ; Sissy M. Jhiang ; Dehua Pei
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：February 15, 2013
• 年：2013
• 卷：8
• 期：2
• 页码：423-431
• 全文大小：387K
• 年卷期：v.8,no.2(February 15, 2013)
• ISSN：1554-8937

文摘

Cyclic peptides hold great potential as therapeutic agents and research tools, but their broad application has been limited by poor membrane permeability. Here, we report a potentially general approach for intracellular delivery of cyclic peptides. Short peptide motifs rich in arginine and hydrophobic residues (e.g., F桅RRRR, where 桅 is l-2-naphthylalanine), when embedded into small- to medium-sized cyclic peptides (7鈥?3 amino acids), bound to the plasma membrane of mammalian cultured cells and were subsequently internalized by the cells. Confocal microscopy and a newly developed peptide internalization assay demonstrated that cyclic peptides containing these transporter motifs were translocated into the cytoplasm and nucleus at efficiencies 2鈥?-fold higher than that of nonaarginine (R₉). Furthermore, incorporation of the F桅RRRR motif into a cyclic peptide containing a phosphocoumaryl aminopropionic acid (pCAP) residue generated a cell permeable, fluorogenic probe for detecting intracellular protein tyrosine phosphatase activities.