Most of the reported arginine-rich cell-penetrating peptides (CPPs) for enhancing the drug delivery are linear peptides, and have more than seven arginines to retain the cell penetration properties. Herein, we synthesized a number of polyarginine peptides (R5 and R6) as template CPPs, and explored the effect of acylation and cyclization. The molecular transporter property of acylated cyclic R5 (e.g., dodecanoyl-[R5]) was compared with those of acylated linear R5 (e.g., dodecanoyl-(R5)) and unmodified cyclic R5 ([R5]) (10 �M) using flow cytometry. The combination of acylation and cyclization enhanced the cellular uptake of a fluorescence-labeled phosphopeptide (F-GpYEEI) (5 �M) in human SK-OV-3 cancer cell lines by three-fold, showing higher uptake than heptaarginine (R7) and TAT peptides. The hydrophobic dedecanoyl moiety improved the uptake, possibly through interaction with the phospholipids in the cell membrane. Both dodecanoyl-[R5] and dodecanoyl-[R6] showed potent antibacterial activities against Staphylococcus aureus ATCC 29213 with MIC values of 4.3-4.9 ng/mL.

Acylated cyclic polyarginine cell-penetrating peptides as molecular transporters and antibacterial agents

244th National Meeting (2012)

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