We have previously shown that cyclic peptide [WR]5 significantly improved the cellular uptake of a number of anti-HIV and anti-cancer drugs. A number of cyclic peptides containing arginine, lysine and tryptophan residues, namely [RK]4W4, [W5K]R5, [WK]4R4, and [R5K]W5 were synthesized through Fmoc-solid based chemistry and compared with [WR]5. Among all the peptides, [R5K]W5 significantly improved fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) uptake by 27 folds when compared with F′-GpYEEI and 3 folds when compared with [WR]5 in human leukemia cancer (CCRF-CEM) cells. The peptides were not toxic to the normal kidney cells (LLCPK) at a concentration of 50 μM. [R5K]W5 decreased the cell viability in CCRF-CEM cells by 2.5 fold at a concentration of 50 μM. The presence of positively charged residues on the ring and hydrophobic residues in a sequential linear outside the ring was an optimal approach for generating compounds with more molecular transporter properties.

Design and evaluation of cyclic peptides containing arginine, lysine and tryptophan residues as a cellular drug delivery system and establishing structure-activity relationship

253rd National Meeting (2017)

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