Design, Synthesis, and Evaluation of Homochiral Peptides Containing Arginine and Histidine as Molecular Transporters.

摘要: Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine histidine residues were synthesized. The showed 0–15% cytotoxicity at 5–100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity leukemia cancer cell line (CCRF-CEM). Among all peptides, [HR]4 peptide was able to improve the delivery of a impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids different alkyl chain length attached N-terminal linear (HR)4 molecular transporter property. Addition fatty acyl chains expected help with permeation through membrane. Thus, we synthesized seven derivatives peptide. using Fmoc/tBu solid phase chemistry, purified reverse-phase high-performance liquid chromatography (RP-HPLC) characterized matrix-assisted laser desorption/ionization (MALDI) spectrometry. C8, C12, C14, C18 did not show on SK-OV-3 or CCRF-CEM lines up 50 concentration; however, higher concentration (100 µM), mild cytotoxicity. For example, C16-(HR)4 also found reduce proliferation 11% C20-(HR)4 10 µM, reducing 21%. Increase lines. better efficiency translocation F′-GpYEEI than alone. Further investigation efficacy that could deliver doxorubicin epirubicin into improved drug antiproliferative ability. These studies provided insights understanding structural requirements for optimal cellular acyl-(HR)4 conjugates.