文摘
Gaegurin 5 is a 24-residue, membrane-active antimicrobial peptide isolated from the skin of an Asian frog,Rana rugosa. We recently reported the antimicrobial activities of two novel undecapeptides derived froman inactive N-terminal fragment (residues 1-11) of gaegurin 5 (Won, et al. J. Biol. Chem. 2004, 279, 14784-14791). In the present work, the anticancer activities of the two antimicrobial undecapeptide analogueswere additionally identified. The relationships between their structural properties and biological activitieswere assessed by characterizing the fundamental structural determinant for the basic membrane interaction.The circular dichroism and nuclear magnetic resonance results revealed that in a membrane-mimeticenvironment, the active peptides adopt a more stabilized helical conformation than that of the inactivefragment, and this conformation conferred an overall amphipathicity to the active peptides. Therefore, themost decisive factor responsible for the activity and selectivity could be the intramolecular amphipathiccooperativity, rather than the amphipathicity itself. Especially, the tryptophan residue of the active peptidesseems to play a crucial role at the critical amphipathic interface that promotes and balances the amphipathiccooperativity by stabilizing both the hydrophilic and hydrophobic interactions with the membrane. Altogether,the present results suggest that the two novel undecapeptides are worthy of therapeutic development as newantibiotic and anticancer agents and provide structural information about their action mechanism.