Mechanism of antibacterial action of a synthetic peptide with an Ala-peptoid residue based on the scorpion-derived antimicrobial peptide IsCT.
A novel bacterial cell-selective antimicrobial peptide, IsCT-P (ILKKIWKPIKKLF-NH(2)), was designed based on the scorpion-derived alpha-helical antimicrobial peptide, IsCT. Here, we investigated the effect of substituting Pro(8) of IsCT-P with the Ala-peptoid residue (N-methylglycine) on the peptide's structure and mechanism of action. Circular dichroism analysis revealed that the modified peptide, IsCT-a, has a much lower alpha-helicity than IsCT-P in membrane mimicking conditions, suggesting the peptoid residue provides much more structural flexibility than the proline residue. IsCT-a was also much less effective than IsCT-P at causing leakage of fluorescent dye entrapped within negatively charged vesicles and at dissipating the membrane potential of Staphylococcus aureus. Collectively, our results suggest that the antibacterial action of IsCT-a is due to the inhibition of intracellular targets rather than the disruption and depolarization of bacterial cell membranes.
Lim
Shin Saeng
SS
Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, Korea.
Yoon
Sang-Pil
SP
Park
Yoonkyoung
Y
Zhu
Wan Long
WL
Park
Il-Seon
IS
Hahm
Kyung-Soo
KS
Shin
Song Yub
SY
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002942:Circular Dichroism; D005452:Fluoresceins / Q000378:metabolism; D053878:Hemolytic Agents / Q000494:pharmacology; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D034444:Peptoids / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000737:chemistry*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D053878:Hemolytic Agents; C435485:IsCT protein, Opisthacanthus madagascariensis; C516429:IsCT-P peptide; D008081:Liposomes; D034444:Peptoids; D012604:Scorpion Venoms; C007740:fluorexon