Development of delivery carriers for plasmid DNA by conjugation of a helical template to oligoarginine. (15th October 2022)

• Record Type: Journal Article
• Authors: Yokoo, Hidetomo; Misawa, Takashi; Kato, Takuma; Tanaka, Masakazu; Demizu, Yosuke; Oba, Makoto
• Is Part Of: Bioorganic & medicinal chemistry. Volume 72(2022)
• Publication Date: 2022-10-15
• Subjects: Cell-penetrating peptide -- Arginine -- Gene transfer -- Non-proteinogenic amino acid -- Plasmid DNA delivery; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.116997
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Arginine (Arg)-rich peptides can penetrate the cell membrane and deliver nucleic acid-based therapeutics into cells. In this study, a helical template designed with a repeating sequence composed of two l -leucines (l -Leu) and a 2-aminoisobutyric acid (Aib) (l -Leu-l -Leu-Aib) was conjugated to nona-arginine on either the C- or N- terminus, designated as Block 1 and Block 2 . Each terminal modification induced helical structure formation and improved the physicochemical properties of peptide/plasmid DNA (pDNA) complexes, resulting in efficient intracellular pDNA delivery. The introduction of a helical template may be effective for the endosomal escape of pDNA and pDNA release from complexes in cells. These results emphasized the potency of a helical template for the development of novel cell-penetrating peptides for pDNA delivery.