title: Aib-containing peptide analogs: cellular uptake and utilization in oligonucleotide delivery.
abstract: α-Aminoisobutyric acid (Aib)-containing peptide analogs derived from TV-XIIa, a cell-penetrating peptide (CPP), were synthesized to explore structure-activity relationships. The replacement of Aib at position 1, 5, or 9 in the TV-XIIa amino acid sequence with alanine (Ala) suppressed the cellular uptake,whereas the simultaneous substitution of the two proline (Pro) residues at positions 6 and 10 with Aib(P-IV) considerably increased the cellular uptake. In order to explore the potential use of the Aib-containing peptide analogs for the cellular delivery of oligonucleotides (ODNs), we synthesized a covalent conjugate (P-IV-AON) of a 15-mer antisense ODN, which is complementary to luciferase gene, with P-IV, and the antisense effect of the P-IV-AON conjugate on luciferase expression in A549 cells was examined. Luciferase expression was decreased in the presence of the conjugate upon treatment with the reaction buffer at the concentrations of 5 and 10 μM.
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Wada
authors.forename: Tomoe
authors.initials: T
authors.lastname: Urase
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kenta
authors.initials: K
authors.lastname: Ban
authors.forename: Aya
authors.initials: A
authors.lastname: Sudani
authors.forename: Yui
authors.initials: Y
authors.lastname: Kawai
authors.forename: Junsuke
authors.initials: J
authors.lastname: Hayashi
authors.forename: Hidehito
authors.initials: H
authors.lastname: Urata
mesh_terms: D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000621:Aminoisobutyric Acids; D057846:Cell-Penetrating Peptides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D010455:Peptides; C100049:2-aminoisobutyric acid; D008156:Luciferases