• BMB Reports
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• v.33 no.1
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• pp.49-53
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• 2000

PMAP-23 is a 23-residue antimicrobial peptide derived from porcine myloid cells. In order to investigate the effects of two Pro residues at positions 12 and 15 of PMAP-23 on antibiotic activity, two analogues in which Ala was substituted for Pro residue at position 12 or 15 were synthesized. $Pro^{12}{\rightarrow}Ala$ (PMAPl) or $Pro^{15}{\rightarrow}Ala$(PMAP2) substitution in PMAP-23 caused a significant reduction on antitumor and phospholipid vesicle-disrupting activities, but did not cause a significant effect on antibacterial activity. PMAP-23 displayed the type I ${\beta}-turn$ structure with a negative ellipticity at near 205 om in SDS micelle, whereas PMAP1 and PMAP2 had a somewhat ${\alpha}-helical$ propensity in TFE solution, as compared to PMAP-23. These results suggest that two Pro residues of positions 12 and 15 in PMAP-23 play important roles in the formation of ${\beta}-turn$ structure on lipid membrane and its ${\beta}-turn$ structure may be essential for antibiotic activity including phospholipid vesicle-disrupting property.

• BMB Reports
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• v.32 no.6
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• pp.561-566
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• 1999

CA(1-8)-ME(1-12) [CA-ME], composed of cecropin A(1-8) and melittin(1-12), is a synthetic antimicrobial peptide having potent antibacterial and antitumor activities with minimal hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly, of CA-ME on antibiotic activity, CA-ME and three analogues, CA-ME1, CA-ME2, and CA-ME3, were synthesized. The Gly-Ile-Gly sequence of Ca-ME was deleted in CA-ME1 and replaced with Pro and Gly-Pro-Gly in CA-ME2 and CA-ME3, respectively. CA-ME1 and CA-ME3 showed a significant decrease in antitumor activity and phospholipid vesicle-disrupting ability. However, CA-ME2 showed similar antitumor and vesicle-disrupting activities, as compared with CA-ME. These results suggest that the flexibility or ${\beta}$-turn induced by Gly-Ile-Gly or Pro in the central part of CA-ME may be important in the electrostatic interaction of the N-terminus cationic ${\alpha}$-helical region with the cell membrane surface and the hydrophobic interaction of the C-terminus amphipathic ${\alpha}$-helical region with the hydrophobic acyl chains in the cell membrane. CA-ME3 exhibited lower antitumor and vesicle-disrupting activities than CA-ME and CA-ME2. This result suggests that the excessive ${\beta}$-turn structure caused by the Gly-Pro-Gly sequence in CA-ME3 seems to interrupt ion channel/pore formation in the lipid bilayer. We concluded that the appropriate flexibility or bilayer. We concluded that the appropriate flexibility or ${\beta}$-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure.