Influence of Aib-Containing Amphipathic Helical Chain Length in MAP(Aib)-cRGD as Carrier for siRNA Delivery.

MAP(Aib)-cRGD, which is a conjugate of an α-aminoisobutyric acid (Aib)-containing amphipathic helical peptide [MAP(Aib)] with a αv β3 integrin binding ligand, cRGD, at the C-terminus of the helical peptide, has been developed for siRNA delivery into cells. In this work, we synthesized three peptides containing 19 (PI), 18 (PII), and 17 (PIII) amino acid residues in the helical peptide, which lack Aib, Leu-Aib, and Lys-Leu-Aib residues present in the C-terminus of the helical peptide of the parent MAP(Aib)-cRGD, respectively. MAP(Aib)-cRGD showed the siRNA delivery into cells and the RNAi effect both in the presence and in the absence of serum in reaction media. In contrast, PI delivered siRNA into cells, and this was followed by the RNAi effect in only serum-free reaction media. On the other hand, siRNA delivery was abolished by the further reduction of the number of residues (PII and PIII) in the C-terminus. Our data indicate that the Aib-containing helical part requires 20 residues in the conjugation of the helical peptide with cRGD for the construction of carrier for siRNA delivery into cells.