Development of 2-aminoisobutyric acid (Aib)-rich cell-penetrating foldamers for efficient siRNA delivery

• Published in: Chemical communications (Cambridge, England) Vol. 55; no. 54; pp. 7792 - 7795
• Main Authors: Misawa, Takashi, Ohoka, Nobumichi, Oba, Makoto, Yamashita, Hiroko, Tanaka, Masakazu, Naito, Mikihiko, Demizu, Yosuke
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 02.07.2019
• Subjects: Amino Acid Sequence; Amino acids; Aminoisobutyric Acids - chemistry; Cell Line, Tumor; Cell-Penetrating Peptides - chemical synthesis; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - metabolism; Cell-Penetrating Peptides - toxicity; chemical compounds; chemical reactions; cytotoxicity; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug Carriers - toxicity; Gene Knockdown Techniques; Gene Silencing; Humans; neoplasm cells; Protein Conformation, alpha-Helical; Protein Engineering - methods; Proto-Oncogene Proteins p21(ras) - genetics; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - genetics; small interfering RNA; Toxicity
• ISSN: 1359-7345; 1364-548X; 1364-548X
• DOI: 10.1039/c9cc02203a

We have designed and synthesized a set of cell-penetrating foldamers (CPFs), Blocks 1-8, composed of the common amino acids Leu, Arg, and Gly, as well as the helicogenic amino acid 2-aminoisobutyric acid. The findings showed that Block 3 could deliver siRNA into cells without significant cytotoxicity. We also demonstrated that Block 3 could be applied to selectively kill the oncogene-driven cancer cells. We have designed and synthesized a set of cell-penetrating foldamers (CPFs), Blocks 1-8, composed of the common amino acids Leu, Arg, and Gly, as well as the helicogenic amino acid 2-aminoisobutyric acid.