Structure-activity relationship of a novel pentapeptide with cancer cell growth-inhibitory activity.
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.
Kamiya
Masakatsu
M
Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan.
Oyauchi
Keisuke
K
Sato
Yoshinori
Y
Yokoyama
Takuya
T
Wang
Mofei
M
Aizawa
Tomoyasu
T
Kumaki
Yasuhiro
Y
Mizuguchi
Mineyuki
M
Imai
Kunio
K
Demura
Makoto
M
Suzuki
Koichi
K
Kawano
Keiichi
K
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D009842:Oligopeptides