Structure-activity relationship study of Aib-containing amphipathic helical peptide-cyclic RGD conjugates as carriers for siRNA delivery.

The conjugation of Aib-containing amphipathic helical peptide with cyclo(-Arg-Gly-Asp- d -Phe-Cys-) (cRGDfC) at the C-terminus of the helix peptide ( PI ) has been reported to be useful for constructing a carrier for targeted siRNA delivery into cells. In order to explore structure–activity relationships for the development of potential carriers for siRNA delivery, we synthesized conjugates of Aib-containing amphipathic helical peptide with cRGDfC at the N-terminus ( PII ) and both the N- and C-termini ( PIII ) of the helical peptide. Furthermore, to examine the influence of PI helical chain length on siRNA delivery, truncated peptides containing 16 ( PIV ), 12 ( PV ), and 8 ( PVI ) amino acid residues at the N-terminus of the helical chain were synthesized. PII and PIII , as well as PI , could deliver anti-luciferase siRNA into cells to induce the knockdown of luciferase stably expressed in cells. In contrast, all of the truncated peptides were unlikely to transport siRNA into cells. [ABSTRACT FROM AUTHOR]