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

• Published in: Journal of peptide science Vol. 16; no. 2; pp. 105 - 109
• Main Authors: Xie, Wenlin, Liu, Jian, Qiu, Minghua, Yuan, Jiancheng, Xu, Anlong
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.02.2010
• Subjects: Amino Acid Sequence; anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; cell-penetrating peptide; Chromatography, High Pressure Liquid; Drug Design; Humans; Liver Neoplasms - drug therapy; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Octreotide; Octreotide - analogs & derivatives; Octreotide - chemistry; Octreotide - pharmacology; Octreotide - therapeutic use; peptide synthesis; Stomach Neoplasms - drug therapy
• ISSN: 1075-2617; 1099-1387
• DOI: 10.1002/psc.1205

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. Four novel octreotide analogs with Cell‐Penetrating Peptide (CPPs) at the N‐terminus or C‐terminus were synthesized. The antiproliferative activity of the analogs was tested in vitro on human gastric (SGC‐7901) and hepatocellular cancer (BEL7402) cell lines using the MTT assay. Interestingly, these analogs showed a higher anticancer activities than the parent octreotide except CMTPT03 analog. The results demonstrate that the Cell‐Penetrating Peptide can enhance the anti‐proliferative activity of octreotide.