Structure–activity relationship of a novel pentapeptide with cancer cell growth-inhibitory activity

✍ Scribed by Masakatsu Kamiya; Keisuke Oyauchi; Yoshinori Sato; Takuya Yokoyama; Mofei Wang; Tomoyasu Aizawa; Yasuhiro Kumaki; Mineyuki Mizuguchi; Kunio Imai; Makoto Demura; Koichi Suzuki; Keiichi Kawano

• Book ID: 105359855
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 370 KB
• Volume: 16
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1225

✦ Synopsis

Abstract

We previously reported that yamamarin, a pentapeptide with an amidated C‐terminus (DILRG‐NH~2~) isolated from larvae of the silkmoth, and its palmitoylated analog (C16‐DILRG‐NH~2~) suppressed proliferation of rat hepatoma (liver cancer) cells. In this study, we investigated the structure–activity relationship of yamamarin by in vitro assay and spectroscopic methods (CD and NMR) for various analogs. The in vitro assay results demonstrated that the chemical structure of the C‐terminal part (‐RG‐NH~2~) of yamamarin is essential for its activity. The CD and NMR results indicated that yamamarin and its analog adopt predominantly a random coil conformation. Moreover, a comparison of NMR spectra of DILRG‐NH~2~ and C16‐DILRG‐NH~2~ revealed that the N‐terminal palmitoyl group of C16‐DILRG‐NH~2~ did not affect the conformation of the C‐terminal part, which is essential for activity. Together, these results should assist in the design of more sophisticated anticancer drugs. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.