A different molecular mechanism underlying antimicrobial and hemolytic actions of temporins A and L.
In this work, the naturally occurring antimicrobial peptides temporin A (TA) and L (TL) are studied by spectroscopic (CD and NMR) techniques and molecular dynamics simulation. We analyzed the interactions of TA and TL with sodium dodecyl sulfate (SDS) and dodecylphosphocholine (DPC) micelles, which mimic bacterial and mammalian membranes, respectively. In SDS, the peptides prefer a location at the micelle-water interface; in DPC, they prefer a location perpendicular to the micelle surface, with the N-terminus imbedded in the hydrophobic core. TL shows higher propensity, with respect to TA, in forming alpha-helical structures in both membrane mimetic systems and the highest propensity to penetrate the micelles. Hence, we have proposed a different molecular mechanism underlying the antimicrobial and hemolytic activities of the two peptides. We also designed new analogues of TA and TL and found interesting differences in their efficacy against microbial species and human erythrocytes.
Carotenuto
Alfonso
A
Department of Pharmaceutical and Toxicological Chemistry, University of Naples "Federico II", I-80131 Naples, Italy.
Malfi
Stefania
S
Saviello
Maria Rosaria
MR
Campiglia
Pietro
P
Gomez-Monterrey
Isabel
I
Mangoni
Maria Luisa
ML
Gaddi
Ludovica Marcellini Hercolani
LM
Novellino
Ettore
E
Grieco
Paolo
P
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011506:Proteins; C104501:temporin; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine