Aib-containing peptide analogs: Cellular uptake and utilization in oligonucleotide delivery

作者：Wada Shun ichi^*; Urase Tomoe; Hasegawa Yuka; Ban Kenta; Sudani Aya; Kawai Yui; Hayashi Junsuke; Urata Hidehito

来源：Bioorganic & Medicinal Chemistry, 2014, 22(24): 6776-6780.

DOI：10.1016/j.bmc.2014.10.040

• alpha-Aminoisobutyric acid (Aib)
• alpha-Helix
• Cell-penetrating peptide (CPP)
• Antisense oligonucleotide

alpha-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 mu M.

• 出版日期2014-12-15