Development of a Cell-penetrating Peptide that Exhibits Responsive Changes in its Secondary Structure in the Cellular Environment

• DOI: 10.1038/srep33003
• Publication Date: 2016-09-09T09:44:04Z
• Authors: Hiroko Yamashita; Takuma Kato; Makoto Oba; Takashi Misawa; Takayuki Hattori; Nobumichi Ohoka; Masakazu Tanaka; Mikihiko Naito; Masaaki Kurihara; Yosuke Demizu
• Keywords: Cell-penetrating peptide; HeLa; Cationic polymerization; Cell permeability

Abstract Cell-penetrating peptides (CPP) are received a lot of attention as an intracellular delivery tool for hydrophilic molecules such drugs, proteins, and DNAs. We designed synthesized nona-arginine analogues 1 – 5 [FAM-β-Ala-( l -Arg- -Pro) 3 -(Gly) -NH 2 ( ), FAM-β-Ala-( -Pro NH2 ) Gu -Arg) -( 4 - 6 )] containing -proline or cationic proline derivatives investigated their cell-penetrating abilities. Interestingly, only peptide having the side-chain guanidinyl exhibited secondary structural change in cellular environment. Specifically, formed random structure conditions, whereas it helical under amphipathic conditions. Furthermore, during permeability tests, demonstrated greater activity than other effectively transported plasmid DNA into HeLa cells. Thus, -containing may be useful candidate gene carrier.