Effects of tryptophan residues of porcine myeloid antibacterial peptide PMAP-23 on antibiotic activity.
PMAP-23 is a 23-residue antimicrobial peptide from porcine myeloid cells. In order to determine the effects of two Trp residues in positions 7 and 21 of PMAP-23 on antibacterial activity and phospholipid vesicle interacting property, two analogues in which Ala is substituted for Trp residue in position 7 or 21 were synthesized. A(21)-PMAP-23 exhibited reduced antibacterial activity and phospholipid vesicle disrupting activity when compared to those of PMAP-23 and A(7)-PMAP-23. PMAP-23 readily interacted with model lipid membrane and induced membrane destabilization. Therefore antibacterial activity induced by PMAP-23 is due to the interaction of cell membrane with peptide followed by membrane perturbation. A significant structural change on the SDS micelle was not found by Ala substitution of the Trp residue of PMAP-23. Also, there is a good correlation between hydrophobic interaction on RP-HPLC, expressed as retention time on RP-HPLC, and antibacterial activity. The vesicle titration experiment indicated that Trp residues located at near C-terminus are accessible to hydrophobic tail of phospholipid vesicle. This result suggests that the C-terminal end of PMAP-23 penetrates into the lipid bilayer in the course of the interaction with phospholipid membranes and is important for its antibacterial activity.
Kang
J H
JH
Peptide Engineering Research Unit, Korea Research Institute of Bioscience and Biotechnology, Taejon, 305-600, Korea.
Shin
S Y
SY
Jang
S Y
SY
Kim
K L
KL
Hahm
K S
KS
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005453:Fluorescence; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D013552:Swine; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology*
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D010455:Peptides; D010743:Phospholipids; C086301:porcine myeloid antibacterial peptide 23; D014364:Tryptophan