Cellular internalization of water-soluble helical aromatic amide foldamers.
The intracellular transport of drugs and therapeutics represents one of the most exciting and challenging areas at the interface of chemistry, biology, and medicine. Most of the effort in this field so far has been devoted to the development of peptide-based delivery systems that can translocate therapeutic agents into their intracellular targets. More recently, the use of bioinspired non-natural foldamers has resulted in the successful delivery of cargo molecules, which possess a wide range of sizes and physicochemical properties across the cell membrane. We report herein the synthesis of aromatic amide foldamers and their biological evaluation as cell-penetrating agents. By using a well-established synthetic route, a series of fluorescein-labeled cationic aryl amide conjugates has been constructed, and their cellular uptake into various human cell lines has been analyzed by flow cytometry and fluorescence microscopy. The assays revealed that longer oligomers achieve greater cellular translocation, with octamer Q8 proving to be a remarkable vehicle for all three cell lines. Biological studies have also indicated that these helices are biocompatible, thus showing promise in their application as cell-penetrating agents and as vehicles to deliver biologically active molecules into cells.
Iriondo-Alberdi
Jone
J
Université de Bordeaux-CNRS UMR5248, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, 33607 Pessac, France.
Laxmi-Reddy
Katta
K
Bouguerne
Benaissa
B
Staedel
Cathy
C
Huc
Ivan
I
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry*; D002470:Cell Survival / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000577:Amides; D010455:Peptides