Design, synthesis and biological activity of cell‐penetrating peptide‐modified octreotide analogs

Four novel octreotide analogs with cell-penetrating peptides (CPPs) at the N-terminus or C-terminus were synthesized by a stepwise Fmoc solid-phase synthesis strategy. The synthesized peptides were analyzed and characterized using reverse phase HPLC and MALDI-TOF mass spectrometry. The antiproliferative activity of the analogs was tested in vitro on human gastric (SGC-7901) and hepatocellular cancer (BEL7402) cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Interestingly, these analogs showed a higher anticancer activities than the parent octreotide except CMTPT03 analog. The results demonstrate that the designed octreotide analogs enhance their anticancer activity after linking together the CPPs to octreotide at the N-terminus, and are potential molecules for future use in cancer therapy and drug targeting. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.