Effect of dimerization of a beta-turn antimicrobial peptide, PST13-RK, on antimicrobial activity and mammalian cell toxicity.
PST13-RK (KKKFPWWWPFKKK-NH(2)) is an improved derivative of tritrpticin adopting a beta-turn structure. In order to investigate the effect of dimerization of PST13-RK on antimicrobial activity and mammalian cell toxicity, we designed and synthesized its Cys- and Lys-linked dimers. The dimerization of PST13-RK resulted in a 2-4 fold decreased antimicrobial activity against Gram-positive and Gram-negative bacteria. However, the dimers showed a large increase in mammalian cell toxicity against mouse NIH-3T3, human MDA-MB-361, and human A549 cells. These results suggested that PST13-RK is active as a monomer to bacterial cells but as an oligomer to mammalian cells. Since the dimeric PST13-RK is much more effective against the cancer cells than the monomer, it might be an attractive candidate for anticancer chemotherapeutic drugs.
Yang
Sung-Tae
ST
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Korea.
Kim
Jae Il
JI
Shin
Song Yub
SY
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D019281:Dimerization; D006801:Humans; D051379:Mice
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides